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Ritter, A.;  Kreis, N.;  Hoock, S.C.;  Solbach, C.;  Louwen, F.;  Yuan, J. Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Breast Cancer. Encyclopedia. Available online: (accessed on 17 April 2024).
Ritter A,  Kreis N,  Hoock SC,  Solbach C,  Louwen F,  Yuan J. Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Breast Cancer. Encyclopedia. Available at: Accessed April 17, 2024.
Ritter, Andreas, Nina-Naomi Kreis, Samira Catharina Hoock, Christine Solbach, Frank Louwen, Juping Yuan. "Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Breast Cancer" Encyclopedia, (accessed April 17, 2024).
Ritter, A.,  Kreis, N.,  Hoock, S.C.,  Solbach, C.,  Louwen, F., & Yuan, J. (2022, August 25). Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Breast Cancer. In Encyclopedia.
Ritter, Andreas, et al. "Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Breast Cancer." Encyclopedia. Web. 25 August, 2022.
Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Breast Cancer

Breast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Adipose tissue is the major microenvironment of breast cancer. Obesity changes the composition, structure, and function of adipose tissue, which is associated with inflammation and metabolic dysfunction. Interestingly, adipose tissue is rich in ASCs/MSCs, and obesity alters the properties and functions of these cells. As a key component of the mammary stroma, ASCs play essential roles in the breast cancer microenvironment. The crosstalk between ASCs and breast cancer cells is multilateral and can occur both directly through cell–cell contact and indirectly via the secretome released by ASC/MSC, which is considered to be the main effector of their supportive, angiogenic, and immunomodulatory functions. 

ASCs/MSCs obesity breast cancer tumor microenvironment cancer-associated fibroblasts cancer-associated stem cells epithelial–mesenchymal transition therapy resistance

1. Introduction

The prevalence of obesity has tripled during the last decades, posing a major challenge to the entire society and health care systems worldwide [1][2][3]. Obesity, a condition of increased adiposity resulting from an imbalance between food intake and energy expenditure [4], is categorized according to body mass index (BMI) ≥30 kg/m2 [5]. Obesity associates with multiple disorders, including diabetes, hypertension, and cardiovascular diseases [6]. In addition, it is characterized by an increased incidence of cancer in various organs, such as the colon, rectum, kidney, pancreas, gallbladder, liver, thyroid, breast, ovary, and endometrium [7][8][9]. Obesity associates with inflammation and metabolic dysfunction, which greatly promote cancer development. Among various adipose tissue cell types, adipose tissue-derived mesenchymal stromal/stem cells (ASCs), belonging to mesenchymal stromal/stem cells (MSCs), are dramatically altered during obesity progression [10]. Obesity-associated ASCs are of crucial importance, contributing to the establishment of the breast cancer microenvironment and promoting the progression of breast cancer.

2. Crosstalk between ASCs and Breast Cancer Cells

The crosstalk between ASCs and breast cancer cells can occur directly via cell–cell interaction and indirectly via the secretome released by the cells. Cancer cells secrete numerous chemotaxis signals [11], which recruit ASCs from local adipose tissues as well as MSCs from bone marrow into malignant tissue [12]. Cancer-educated ASCs/MSCs may differentiate into cancer-associated ASCs/MSCs or cancer-associated fibroblasts (CAFs) [13]. These ASCs/MSCs in turn promote breast cancer progression [14]. In particular, the ASC/MSC secretome, which is composed of a large number of secreted proteins, peptides and extracellular vesicles (EVs), is considered to be the main effector of their regenerative, tropic, trophic, angiogenic, and immunomodulatory functions.
Regarding the indirect manner, both breast cancer cells and ASCs/MSCs are potent in secreting a large number of soluble bioactive factors [13][15]. In particular, MSCs have the ability to migrate into malignant areas and stimulate cancer development by secreting a range of paracrine factors such as chemokines C-X-C ligand 1 (CXCL1), CXCL2, CXCL5, CXCL7, and CXCL12/stromal-cell-derived factor 1 (SDF1); cytokines such as IL6, IL8, and transforming growth factor β (TGFβ); and growth factors including epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1), and vascular endothelial growth factor (VEGF) [13][16][17]. It has been shown that MSCs facilitate angiogenesis by paracrine secretion of angiogenic growth factors such as platelet-derived growth factor (PDGF) and VEGF [16][18]. Researchers' own studies also demonstrate that ASCs isolated from subcutaneous as well as visceral adipose tissue released numerous cytokines, chemokines, and growth factors involved in inflammation, angiogenesis, and cell migration and proliferation, such as IL6, IL8, TNFα, CXCL1/2/3, CXCL5, monocyte chemotactic and activating factor (CCL2), and EGF [19][20][21].
Moreover, both breast cancer cells and MSC/ASC-derived EVs are essential for the crosstalk between MSCs/ASCs and breast cancer cells [15][22][23]. EVs are a heterogeneous group of membrane-bound vesicles released from cells by invagination and budding. They facilitate cell-to-cell interactions via contact with neighboring cells or internalization by recipient cells, which includes fusion with membrane and endocytosis [24]. According to the biogenesis, biophysical properties, and function, EVs can be classified into three main subtypes, namely exosomes (30–150 nm), microvesicles (MVs) (50–1000 nm), and apoptotic blebs (1000–5000 nm) [25]. Among these EVs, exosomes and MVs are of particular importance in cell–cell communication [25]. Both of them contain lipids, proteins, and genetic material, such as DNA, messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNAs (lncRNA) that can be delivered to and reprogram the recipient cells [26]. Studies have shown that MSC/ASC-EVs exert both inhibitory and promoting effects in several situations and different stages of breast cancer. Through the transfer of various tumor-related factors, EVs promote proliferation, angiogenesis, metastasis, and drug resistance of malignant tumor cells [27][28], as shown in breast cancer cells stimulated with Her2-loaded EVs [27]. These data suggest that ASCs/MSCs may secrete molecules that act in concert with the secretome of breast cancer cells to remodel the microenvironment.
The direct crosstalk between ASCs and breast cancer cells is strictly dependent on their close contact that is established in the TME. Interestingly, tunneling nanotubes (TNTs) have emerged as a new important means of cell–cell communication. TNTs are thin membrane protrusions that connect cells over long distances allowing the exchange of various cellular components, including organelles, proteins, calcium ions, viruses, and bacteria [29]. Notably, TNTs are able to connect multiple cells forming functional cellular networks [30]. TNTs are therefore considered as novel bridges of intercellular communication in physiological and pathological cell processes [31]. Interestingly, MSCs have been shown to form TNTs and transfer mitochondria and other components to target cells [32][33][34]. This occurs under both physiological and pathological conditions, where cells are under stress, leading to changes in cellular energy metabolism and functions [31]. In this context, it is feasible to hypothesize that the protective role of ASCs/MSCs in breast cancer cell survival may be partially mediated through the formation of TNTs, in particular, when breast cancer cells are under stress from chemotherapy or radiotherapy.
Moreover, the activation of several signaling pathways requires direct cell–cell contact via their membrane-bound ligands and receptors, such as the canonical Notch signaling pathway [35]. Notch signaling is linked to the maintenance of breast cancer stem cells [36] and induction of epithelial-to-mesenchymal transition (EMT) resulting in an increase in migration and invasion of breast cancer cells [37]. In fact, direct co-culture of obese ASCs enhanced Notch signaling in ER+ breast cancer cells co-responsible for radiation resistance [38].
Finally, cell–cell fusion, a process that merges the lipid bilayers of two different cells, plays a crucial role during embryonic development as well as in tissue regeneration [39][40]. Studies also provide evidence that cell–cell fusion is closely related to cancer development and metastasis [41]. Although this highly regulated process is not yet fully understood, bone-marrow-derived cells were reported to be able to fuse to cancer cells, and the fused hybrids acquired more malignant characteristics and enhanced self-renewal ability [42]. In line with this observation, MSCs were reported to fuse with diverse malignant cells to promote proliferation and metastasis, including with lung cancer cells [43], liver cancer cells [44], and gastric cancer cells [45]. In particular, it was demonstrated that MSCs were fused with breast cancer cells and promoted their metastatic capacity [46]. Recently, is has been revealed that ASCs are able to fuse spontaneously with breast cancer cells, where breast cancer stem cell (CSC) markers CD44+CD24/lowEpCAM+ are enriched in this fused population [47]. These studies suggest cell fusion as a direct interaction between ASCs/MSCs and cancer cells. Further investigations are needed to explore the molecular mechanisms by which ASCs/MSCs and malignant cells are able to fuse and how this process promotes malignancy.
In sum, as illustrated in Figure 1, the crosstalk between ASCs/MSCs and breast cancer cells is multilateral and majorly mediated by indirect patterns such as the secretion of soluble bioactive factors and EVs released by ASCs as well as breast cancer cells. Although observed mainly in vitro, the interaction of breast cancer cells with ASCs/MSCs may be supported by direct cell–cell contacts including the formation of TNTs, binding of membrane-bound ligands to receptors, and cell–cell fusion. These communications may reshape the TME and fuel breast cancer progression and therapy resistance.
Figure 1. Simplified model representing the crosstalk between ASCs/MSCs and breast cancer cells. The communication between ASCs/MSCs and breast cancer cells may occur directly via cell–cell contact, namely TNTs, cell fusion, and the binding of membrane-bound ligands to receptors, or indirectly via released soluble bioactive factors such as cytokines, chemokines, and growth factors, and EVs including exosomes and microvesicles. EV, extracellular vesicles; ASCs, adipose tissue-derived mesenchymal stromal/stem cells; MSCs, mesenchymal stromal/stem cells; mRNA, messenger RNA; miRNA, microRNA; lncRNA, long non-coding RNA; TNTs, tunneling nanotubes.

3. Mutual Interaction between ASCs/MSCs and Breast Cancer Cells

The communication between MSCs/ASCs and breast cancer cells has been an intensive research focus. The related studies are mostly performed using in vitro models to investigate the effects of ASCs/MSCs or their conditioned medium on proliferation, survival, migration, and invasion of breast cancer cell lines. Breast cancer cell lines are classified based on the status of three important cell surface receptors conventionally used for breast cancer subtyping, ER, PR, and HER2 [48]. Most studies used the following breast cancer cell lines: low metastatic breast cancer cell line BT474 (ER+, PR+, HER2+), MCF-7 (ER+, PR+, HER2) and T47D (ER+, PR+, HER2), metastatic breast cancer cell lines HCC1954 (ER, PR, HER2+, with wild type breast cancer gene 1 (BRCA1)), SKBR3 (ER, PR, HER2+, with wild type BRCA1), and MDA-MB-453 (ER, PR, HER2+, with wild type BRCA1), and highly metastatic breast cancer cell lines MDA-MB-231 (triple negative, with wild type BRCA1), MDA-MB-468 (triple negative, with wild type BRCA1), MDA-MB-436 (triple negative, mutated BRCA1), and SUM149 (triple negative, mutated BRCA1) [48]. Regarding ASCs/MSCs, while tumor adjacent cells [49] or “cancer-educated” MSCs [50] were recently used, most of the studies employed ASCs/MSCs isolated from non-breast sources, including abdominal adipose tissue, bone marrow, and peripheral blood [16][19][51]. It is well-known that ASCs/MSCs from different tissues and organs have distinct transcriptomic, biochemical, and secretory profiles, as well as biologic functions in tissue-specific homeostasis, immune modulation, and vasculogenesis/angiogenesis [52]. This, together with other diversities, such as different BMI, varied donor age, variable ASC/MSC passages, and individual experiment settings, often leads to inconclusive results with breast-cancer-supportive and -suppressive functions [16][53], which may not reflect the situation in vivo in breast cancer tissue.

3.1. ASCs/MSCs Influence Breast Cancer and Related Molecular Mechanisms

Much attention has been paid to elucidating how ASCs/MSCs impact breast cancer cells as well as their TME (Table 1). Although their exact roles are not yet completely understood, ASCs/MSCs are described as both pro- or anti-tumorigenic, depending on the type and source of ASCs/MSCs, the use of breast cancer cell lines, and the in vitro or in vivo models. The studies concerning the anti-tumorigenic impact of MSCs are limited. MSCs have been reported to exert their negative impact on breast cancer by impairing angiogenesis via secretion of exosomes [54], reducing migration and invasion via the release of tissue inhibitor of metalloproteinase (TIMPs) [55], and decreasing breast tumor growth via down regulation of the STAT3 signaling pathway [56]. Nevertheless, the majority of studies report pro-tumorigenic effects of ASCs/MSCs on breast cancer cells, which are multilayered, as depicted in Table 1. The related molecular mechanisms are discussed in detail.


  1. Di Cesare, M.; Bentham, J.; Stevens, G.A.; Zhou, B.; Danaei, G.; Lu, Y.; Bixby, H.; Cowan, M.J.; Riley, L.M.; Hajifathalian, K.; et al. Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 2016, 387, 1377–1396.
  2. Bixby, H.; Bentham, J.; Zhou, B.; Di Cesare, M.; Paciorek, C.J.; Bennett, J.E.; Taddei, C.; Stevens, G.A.; Rodriguez-Martinez, A.; Carrillo-Larco, R.M.; et al. Rising rural body-mass index is the main driver of the global obesity epidemic in adults. Nature 2019, 569, 260–264.
  3. Wang, L.M.; Zhou, B.; Zhao, Z.P.; Yang, L.; Zhang, M.; Jiang, Y.; Li, Y.C.; Zhou, M.G.; Wang, L.H.; Huang, Z.J.; et al. Body-mass index and obesity in urban and rural China: Findings from consecutive nationally representative surveys during 2004–18. Lancet 2021, 398, 53–63.
  4. Vaisse, C.; Reiter, J.F.; Berbari, N.F. Cilia and Obesity. Cold Spring Harb. Perspect. Biol. 2017, 9, a028217.
  5. Sung, H.; Siegel, R.L.; Torre, L.A.; Pearson-Stuttard, J.; Islami, F.; Fedewa, S.A.; Sauer, A.G.; Shuval, K.; Gapstur, S.M.; Jacobs, E.J.; et al. Global patterns in excess body weight and the associated cancer burden. CA Cancer J. Clin. 2019, 69, 88–112.
  6. Malik, V.S.; Willet, W.C.; Hu, F.B. Nearly a decade on—Trends, risk factors and policy implications in global obesity. Nat. Rev. Endocrinol. 2020, 16, 615–616.
  7. Bhaskaran, K.; Douglas, I.; Forbes, H.; dos-Santos-Silva, I.; Leon, D.A.; Smeeth, L. Body-mass index and risk of 22 specific cancers: A population-based cohort study of 5.24 million UK adults. Lancet 2014, 384, 755–765.
  8. Donohoe, C.L.; Lysaght, J.; O’Sullivan, J.; Reynolds, J.V. Emerging Concepts Linking Obesity with the Hallmarks of Cancer. Trends Endocrinol. Metab. 2017, 28, 46–62.
  9. Quail, D.F.; Dannenberg, A.J. The obese adipose tissue microenvironment in cancer development and progression. Nat. Rev. Endocrinol. 2019, 15, 139–154.
  10. Louwen, F.; Ritter, A.; Kreis, N.N.; Yuan, J. Insight into the development of obesity: Functional alterations of adipose-derived mesenchymal stem cells. Obes. Rev. 2018, 19, 888–904.
  11. Krueger, T.E.G.; Thorek, D.L.J.; Denmeade, S.R.; Isaacs, J.T.; Brennen, W.N. Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise. Stem Cells Transl. Med. 2018, 7, 651–663.
  12. Kidd, S.; Spaeth, E.; Dembinski, J.L.; Dietrich, M.; Watson, K.; Klopp, A.; Battula, V.L.; Weil, M.; Andreeff, M.; Marini, F.C. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 2009, 27, 2614–2623.
  13. Karnoub, A.E.; Dash, A.B.; Vo, A.P.; Sullivan, A.; Brooks, M.W.; Bell, G.W.; Richardson, A.L.; Polyak, K.; Tubo, R.; Weinberg, R.A. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007, 449, 557–563.
  14. Yu, P.F.; Huang, Y.; Xu, C.L.; Lin, L.Y.; Han, Y.Y.; Sun, W.H.; Hu, G.H.; Rabson, A.B.; Wang, Y.; Shi, Y.F. Downregulation of CXCL12 in mesenchymal stromal cells by TGFβ promotes breast cancer metastasis. Oncogene 2017, 36, 840–849.
  15. Blache, U.; Horton, E.R.; Xia, T.; Schoof, E.M.; Blicher, L.H.; Schönenberger, A.; Snedeker, J.G.; Martin, I.; Erler, J.T.; Ehrbar, M. Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments. Life Sci. Alliance 2019, 2, e201900304.
  16. Lee, H.Y.; Hong, I.S. Double-edged sword of mesenchymal stem cells: Cancer-promoting versus therapeutic potential. Cancer Sci. 2017, 108, 1939–1946.
  17. El-Haibi, C.P.; Karnoub, A.E. Mesenchymal stem cells in the pathogenesis and therapy of breast cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 399–409.
  18. Papaccio, F.; Paino, F.; Regad, T.; Papaccio, G.; Desiderio, V.; Tirino, V. Concise Review: Cancer Cells, Cancer Stem Cells, and Mesenchymal Stem Cells: Influence in Cancer Development. Stem Cells Transl. Med. 2017, 6, 2115–2125.
  19. Ritter, A.; Friemel, A.; Fornoff, F.; Adjan, M.; Solbach, C.; Yuan, J.; Louwen, F. Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells. Oncotarget 2015, 6, 34475–34493.
  20. Ritter, A.; Friemel, A.; Roth, S.; Kreis, N.N.; Hoock, S.C.; Safdar, B.K.; Fischer, K.; Möllmann, C.; Solbach, C.; Louwen, F.; et al. Subcutaneous and Visceral Adipose-Derived Mesenchymal Stem Cells: Commonality and Diversity. Cells 2019, 8, 1288.
  21. Ritter, A.; Kreis, N.-N.; Roth, S.; Friemel, A.; Jennewein, L.; Eichbaum, C.; Solbach, C.; Louwen, F.; Yuan, J. Restoration of primary cilia in obese adipose-derived mesenchymal stem cells by inhibiting Aurora A or extracellular signal-regulated kinase. Stem Cell Res. Ther. 2019, 10, 255.
  22. Guo, Y.; Zhai, Y.; Wu, L.; Wang, Y.; Wu, P.; Xiong, L. Mesenchymal Stem Cell-Derived Extracellular Vesicles: Pleiotropic Impacts on Breast Cancer Occurrence, Development, and Therapy. Int. J. Mol. Sci. 2022, 23, 2927.
  23. Dong, M.; Liu, Q.; Xu, Y.; Zhang, Q. Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer. Front. Cell Dev. Biol. 2022, 10, 842898.
  24. Abels, E.R.; Breakefield, X.O. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell. Mol. Neurobiol. 2016, 36, 301–312.
  25. Doyle, L.M.; Wang, M.Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 2019, 8, 727.
  26. Kletukhina, S.; Neustroeva, O.; James, V.; Rizvanov, A.; Gomzikova, M. Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Epithelial-Mesenchymal Transition. Int. J. Mol. Sci. 2019, 20, 4813.
  27. Ciravolo, V.; Huber, V.; Ghedini, G.C.; Venturelli, E.; Bianchi, F.; Campiglio, M.; Morelli, D.; Villa, A.; Della Mina, P.; Menard, S.; et al. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J. Cell. Physiol. 2012, 227, 658–667.
  28. Tourneur, L.; Mistou, S.; Schmitt, A.; Chiocchia, G. Adenosine receptors control a new pathway of Fas-associated death domain protein expression regulation by secretion. J. Biol. Chem. 2008, 283, 17929–17938.
  29. Abounit, S.; Zurzolo, C. Wiring through tunneling nanotubes--from electrical signals to organelle transfer. J. Cell Sci. 2012, 125, 1089–1098.
  30. Ariazi, J.; Benowitz, A.; De Biasi, V.; Den Boer, M.L.; Cherqui, S.; Cui, H.; Douillet, N.; Eugenin, E.A.; Favre, D.; Goodman, S.; et al. Tunneling Nanotubes and Gap Junctions-Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions. Front. Mol. Neurosci. 2017, 10, 333.
  31. Luchetti, F.; Carloni, S.; Nasoni, M.G.; Reiter, R.J.; Balduini, W. Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery. J. Pineal Res. 2022, 73, e12800.
  32. Spees, J.L.; Olson, S.D.; Whitney, M.J.; Prockop, D.J. Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. USA 2006, 103, 1283–1288.
  33. Liu, K.; Ji, K.; Guo, L.; Wu, W.; Lu, H.; Shan, P.; Yan, C. Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer. Microvasc. Res. 2014, 92, 10–18.
  34. Islam, M.N.; Das, S.R.; Emin, M.T.; Wei, M.; Sun, L.; Westphalen, K.; Rowlands, D.J.; Quadri, S.K.; Bhattacharya, S.; Bhattacharya, J. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat. Med. 2012, 18, 759–765.
  35. Kopan, R.; Ilagan, M.X. The canonical Notch signaling pathway: Unfolding the activation mechanism. Cell 2009, 137, 216–233.
  36. Yuan, X.; Zhang, M.; Wu, H.; Xu, H.; Han, N.; Chu, Q.; Yu, S.; Chen, Y.; Wu, K. Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis. PLoS ONE 2015, 10, e0131689.
  37. Shao, S.; Zhao, X.; Zhang, X.; Luo, M.; Zuo, X.; Huang, S.; Wang, Y.; Gu, S.; Zhao, X. Notch1 signaling regulates the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner. Mol. Cancer 2015, 14, 28.
  38. Sabol, R.A.; Villela, V.A.; Denys, A.; Freeman, B.T.; Hartono, A.B.; Wise, R.M.; Harrison, M.A.A.; Sandler, M.B.; Hossain, F.; Miele, L.; et al. Obesity-Altered Adipose Stem Cells Promote Radiation Resistance of Estrogen Receptor Positive Breast Cancer through Paracrine Signaling. Int. J. Mol. Sci. 2020, 21, 2722.
  39. Aguilar, P.S.; Baylies, M.K.; Fleissner, A.; Helming, L.; Inoue, N.; Podbilewicz, B.; Wang, H.; Wong, M. Genetic basis of cell-cell fusion mechanisms. Trends Genet. TIG 2013, 29, 427–437.
  40. Alvarez-Dolado, M.; Martínez-Losa, M. Cell fusion and tissue regeneration. Adv. Exp. Med. Biol. 2011, 713, 161–175.
  41. Zhou, X.; Merchak, K.; Lee, W.; Grande, J.P.; Cascalho, M.; Platt, J.L. Cell Fusion Connects Oncogenesis with Tumor Evolution. Am. J. Pathol. 2015, 185, 2049–2060.
  42. Dittmar, T.; Nagler, C.; Niggemann, B.; Zänker, K.S. The dark side of stem cells: Triggering cancer progression by cell fusion. Curr. Mol. Med. 2013, 13, 735–750.
  43. Xu, M.H.; Gao, X.; Luo, D.; Zhou, X.D.; Xiong, W.; Liu, G.X. EMT and acquisition of stem cell-like properties are involved in spontaneous formation of tumorigenic hybrids between lung cancer and bone marrow-derived mesenchymal stem cells. PLoS ONE 2014, 9, e87893.
  44. Li, H.; Feng, Z.; Tsang, T.C.; Tang, T.; Jia, X.; He, X.; Pennington, M.E.; Badowski, M.S.; Liu, A.K.; Chen, D.; et al. Fusion of HepG2 cells with mesenchymal stem cells increases cancer-associated and malignant properties: An in vivo metastasis model. Oncol. Rep. 2014, 32, 539–547.
  45. Xue, J.; Zhu, Y.; Sun, Z.; Ji, R.; Zhang, X.; Xu, W.; Yuan, X.; Zhang, B.; Yan, Y.; Yin, L.; et al. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness. BMC Cancer 2015, 15, 793.
  46. Melzer, C.; von der Ohe, J.; Hass, R. Enhanced metastatic capacity of breast cancer cells after interaction and hybrid formation with mesenchymal stroma/stem cells (MSC). Cell Commun. Signal. 2018, 16, 2.
  47. Chan, Y.W.; So, C.; Yau, K.L.; Chiu, K.C.; Wang, X.; Chan, F.L.; Tsang, S.Y. Adipose-derived stem cells and cancer cells fuse to generate cancer stem cell-like cells with increased tumorigenicity. J. Cell. Physiol. 2020, 235, 6794–6807.
  48. Dai, X.; Cheng, H.; Bai, Z.; Li, J. Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping. J. Cancer 2017, 8, 3131–3141.
  49. Jotzu, C.; Alt, E.; Welte, G.; Li, J.; Hennessy, B.T.; Devarajan, E.; Krishnappa, S.; Pinilla, S.; Droll, L.; Song, Y.H. Adipose tissue derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor derived factors. Cell. Oncol. 2011, 34, 55–67.
  50. Sai, B.Q.; Dai, Y.F.; Fan, S.Q.; Wang, F.; Wang, L.J.; Li, Z.; Tang, J.Q.; Wang, L.; Zhang, X.N.; Zheng, L.L.; et al. Cancer-educated mesenchymal stem cells promote the survival of cancer cells at primary and distant metastatic sites via the expansion of bone marrow-derived-PMN-MDSCs. Cell Death Dis. 2019, 10, 941.
  51. Najar, M.; Fayyad-Kazan, H.; Faour, W.H.; Badran, B.; Journe, F.; Lagneaux, L. Breast cancer cells and bone marrow mesenchymal stromal cells: A regulated modulation of the breast tumor in the context of immune response. Inflamm. Res. 2017, 66, 129–139.
  52. Cho, K.A.; Park, M.; Kim, Y.H.; Woo, S.Y.; Ryu, K.H. RNA sequencing reveals a transcriptomic portrait of human mesenchymal stem cells from bone marrow, adipose tissue, and palatine tonsils. Sci. Rep. 2017, 7, 17114.
  53. Lin, W.; Huang, L.; Li, Y.; Fang, B.; Li, G.; Chen, L.; Xu, L. Mesenchymal Stem Cells and Cancer: Clinical Challenges and Opportunities. BioMed Res. Int. 2019, 2019, 2820853.
  54. Lee, J.K.; Park, S.R.; Jung, B.K.; Jeon, Y.K.; Lee, Y.S.; Kim, M.K.; Kim, Y.G.; Jang, J.Y.; Kim, C.W. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS ONE 2013, 8, e84256.
  55. Clarke, M.R.; Imhoff, F.M.; Baird, S.K. Mesenchymal stem cells inhibit breast cancer cell migration and invasion through secretion of tissue inhibitor of metalloproteinase-1 and -2. Mol. Carcinog. 2015, 54, 1214–1219.
  56. He, N.; Kong, Y.; Lei, X.; Liu, Y.; Wang, J.; Xu, C.; Wang, Y.; Du, L.; Ji, K.; Wang, Q.; et al. MSCs inhibit tumor progression and enhance radiosensitivity of breast cancer cells by down-regulating Stat3 signaling pathway. Cell Death Dis. 2018, 9, 1026.
  57. Yang, H.Y.; Qu, R.M.; Lin, X.S.; Liu, T.X.; Sun, Q.Q.; Yang, C.; Li, X.H.; Lu, W.; Hu, X.F.; Dai, J.X.; et al. IGF-1 from adipose-derived mesenchymal stem cells promotes radioresistance of breast cancer cells. Asian Pac. J. Cancer Prev. APJCP 2014, 15, 10115–10119.
  58. De Luca, A.; Lamura, L.; Gallo, M.; Maffia, V.; Normanno, N. Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth factor promote breast cancer cell migration. J. Cell. Biochem. 2012, 113, 3363–3370.
  59. Xu, H.; Zhou, Y.; Li, W.; Zhang, B.; Zhang, H.; Zhao, S.; Zheng, P.; Wu, H.; Yang, J. Tumor-derived mesenchymal-stem-cell-secreted IL-6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer. Oncol. Lett. 2018, 15, 9142–9150.
  60. Yan, X.-L.; Fu, C.-J.; Chen, L.; Qin, J.-H.; Zeng, Q.; Yuan, H.-F.; Nan, X.; Chen, H.-X.; Zhou, J.-N.; Lin, Y.-L.; et al. Mesenchymal stem cells from primary breast cancer tissue promote cancer proliferation and enhance mammosphere formation partially via EGF/EGFR/Akt pathway. Breast Cancer Res. Treat. 2012, 132, 153–164.
  61. Devarajan, E.; Song, Y.H.; Krishnappa, S.; Alt, E. Epithelial-mesenchymal transition in breast cancer lines is mediated through PDGF-D released by tissue-resident stem cells. Int. J. Cancer 2012, 131, 1023–1031.
  62. Chen, Y.-C.; Gonzalez, M.E.; Burman, B.; Zhao, X.; Anwar, T.; Tran, M.; Medhora, N.; Hiziroglu, A.B.; Lee, W.; Cheng, Y.-H.; et al. Mesenchymal Stem/Stromal Cell Engulfment Reveals Metastatic Advantage in Breast Cancer. Cell Rep. 2019, 27, 3916–3926.e15.
  63. Wu, S.; Wang, Y.; Yuan, Z.; Wang, S.; Du, H.; Liu, X.; Wang, Q.; Zhu, X. Human adipose-derived mesenchymal stem cells promote breast cancer MCF7 cell epithelial-mesenchymal transition by cross interacting with the TGF-β/Smad and PI3K/AKT signaling pathways. Mol. Med. Rep. 2019, 19, 177–186.
  64. Su, F.; Wang, X.; Pearson, T.; Lee, J.; Krishnamurthy, S.; Ueno, N.T.; Kolonin, M.G. Ablation of Stromal Cells with a Targeted Proapoptotic Peptide Suppresses Cancer Chemotherapy Resistance and Metastasis. Mol. Ther. Oncolytics 2020, 18, 579–586.
  65. Razmkhah, M.; Jaberipour, M.; Erfani, N.; Habibagahi, M.; Talei, A.R.; Ghaderi, A. Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: Do they protect breast cancer cells from the immune response? Cell. Immunol. 2011, 266, 116–122.
  66. Sepehr, K.S.; Razavi, A.; Hassan, Z.M.; Fazel, A.; Abdollahpour-Alitappeh, M.; Mossahebi-Mohammadi, M.; Yekaninejad, M.S.; Farhadihosseinabadi, B.; Hashemi, S.M. Comparative immunomodulatory properties of mesenchymal stem cells derived from human breast tumor and normal breast adipose tissue. Cancer Immunol. Immunother. 2020, 69, 1841–1854.
  67. Mehdipour, F.; Razmkhah, M.; Rezaeifard, S.; Bagheri, M.; Talei, A.-R.; Khalatbari, B.; Ghaderi, A. Mesenchymal stem cells induced anti-inflammatory features in B cells from breast tumor draining lymph nodes. Cell Biol. Int. 2018, 42, 1658–1669.
  68. Zaoui, M.; Morel, M.; Ferrand, N.; Fellahi, S.; Bastard, J.P.; Lamazière, A.; Larsen, A.K.; Béréziat, V.; Atlan, M.; Sabbah, M. Breast-Associated Adipocytes Secretome Induce Fatty Acid Uptake and Invasiveness in Breast Cancer Cells via CD36 Independently of Body Mass Index, Menopausal Status and Mammary Density. Cancers 2019, 11, 2012.
  69. Sakurai, M.; Miki, Y.; Takagi, K.; Suzuki, T.; Ishida, T.; Ohuchi, N.; Sasano, H. Interaction with adipocyte stromal cells induces breast cancer malignancy via S100A7 upregulation in breast cancer microenvironment. Breast Cancer Res. 2017, 19, 70.
  70. Ren, G.; Zhao, X.; Wang, Y.; Zhang, X.; Chen, X.; Xu, C.; Yuan, Z.R.; Roberts, A.I.; Zhang, L.; Zheng, B.; et al. CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα. Cell Stem Cell 2012, 11, 812–824.
  71. Yu, P.F.; Huang, Y.; Han, Y.Y.; Lin, L.Y.; Sun, W.H.; Rabson, A.B.; Wang, Y.; Shi, Y.F. TNFα-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2(+) neutrophils. Oncogene 2017, 36, 482–490.
  72. Halpern, J.L.; Kilbarger, A.; Lynch, C.C. Mesenchymal stem cells promote mammary cancer cell migration in vitro via the CXCR2 receptor. Cancer Lett. 2011, 308, 91–99.
  73. Zhang, T.; Lee, Y.W.; Rui, Y.F.; Cheng, T.Y.; Jiang, X.H.; Li, G. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res. Ther. 2013, 4, 70.
  74. Wei, H.-J.; Zeng, R.; Lu, J.-H.; Lai, W.-F.T.; Chen, W.-H.; Liu, H.-Y.; Chang, Y.-T.; Deng, W.-P. Adipose-derived stem cells promote tumor initiation and accelerate tumor growth by interleukin-6 production. Oncotarget 2015, 6, 7713–7726.
  75. Goto, H.; Shimono, Y.; Funakoshi, Y.; Imamura, Y.; Toyoda, M.; Kiyota, N.; Kono, S.; Takao, S.; Mukohara, T.; Minami, H. Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin. Oncogene 2019, 38, 767–779.
  76. Strong, A.L.; Ohlstein, J.F.; Biagas, B.A.; Rhodes, L.V.; Pei, D.T.; Tucker, H.A.; Llamas, C.; Bowles, A.C.; Dutreil, M.F.; Zhang, S.; et al. Leptin produced by obese adipose stromal/stem cells enhances proliferation and metastasis of estrogen receptor positive breast cancers. Breast Cancer Res. 2015, 17, 112.
  77. Strong, A.L.; Strong, T.A.; Rhodes, L.V.; Semon, J.A.; Zhang, X.; Shi, Z.; Zhang, S.; Gimble, J.M.; Burow, M.E.; Bunnell, B.A. Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways. Breast Cancer Res. BCR 2013, 15, R102.
  78. Hillers, L.E.; D’Amato, J.V.; Chamberlin, T.; Paderta, G.; Arendt, L.M. Obesity-Activated Adipose-Derived Stromal Cells Promote Breast Cancer Growth and Invasion. Neoplasia 2018, 20, 1161–1174.
  79. Sabol, R.A.; Bowles, A.C.; Côté, A.; Wise, R.; O’Donnell, B.; Matossian, M.D.; Hossain, F.M.; Burks, H.E.; Del Valle, L.; Miele, L.; et al. Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models. Breast Cancer Res. 2019, 21, 67.
  80. Ling, L.; Mulligan, J.A.; Ouyang, Y.; Shimpi, A.A.; Williams, R.M.; Beeghly, G.F.; Hopkins, B.D.; Spector, J.A.; Adie, S.G.; Fischbach, C. Obesity-associated Adipose Stromal Cells Promote Breast Cancer Invasion Through Direct Cell Contact and ECM Remodeling. Adv. Funct. Mater. 2020, 30, 1910650.
  81. Strong, A.L.; Pei, D.T.; Hurst, C.G.; Gimble, J.M.; Burow, M.E.; Bunnell, B.A. Obesity Enhances the Conversion of Adipose-Derived Stromal/Stem Cells into Carcinoma-Associated Fibroblast Leading to Cancer Cell Proliferation and Progression to an Invasive Phenotype. Stem Cells Int. 2017, 2017, 9216502.
  82. Sabol, R.A.; Beighley, A.; Giacomelli, P.; Wise, R.M.; Harrison, M.A.A.; O’Donnnell, B.A.; Sullivan, B.N.; Lampenfeld, J.D.; Matossian, M.D.; Bratton, M.R.; et al. Obesity-Altered Adipose Stem Cells Promote ER+ Breast Cancer Metastasis through Estrogen Independent Pathways. Int. J. Mol. Sci. 2019, 20, 1419.
  83. Kwon, H.; Pessin, J.E. Adipokines mediate inflammation and insulin resistance. Front. Endocrinol. 2013, 4, 71.
  84. Esquivel-Velázquez, M.; Ostoa-Saloma, P.; Palacios-Arreola, M.I.; Nava-Castro, K.E.; Castro, J.I.; Morales-Montor, J. The role of cytokines in breast cancer development and progression. J. Interferon Cytokine Res. 2015, 35, 1–16.
  85. Manore, S.G.; Doheny, D.L.; Wong, G.L.; Lo, H.-W. IL-6/JAK/STAT3 Signaling in Breast Cancer Metastasis: Biology and Treatment. Front. Oncol. 2022, 12, 866014.
  86. Iyengar, N.M.; Gucalp, A.; Dannenberg, A.J.; Hudis, C.A. Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2016, 34, 4270–4276.
  87. Pileczki, V.; Braicu, C.; Gherman, C.D.; Berindan-Neagoe, I. TNF-α gene knockout in triple negative breast cancer cell line induces apoptosis. Int. J. Mol. Sci. 2012, 14, 411–420.
  88. Kitahara, C.M.; Flint, A.J.; de Gonzalez, A.B.; Bernstein, L.; Brotzman, M.; MacInnis, R.J.; Moore, S.C.; Robien, K.; Rosenberg, P.S.; Singh, P.N.; et al. Association between Class III Obesity (BMI of 40–59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies. PLoS Med. 2014, 11, e1001673.
  89. Obradovic, M.; Sudar-Milovanovic, E.; Soskic, S.; Essack, M.; Arya, S.; Stewart, A.J.; Gojobori, T.; Isenovic, E.R. Leptin and Obesity: Role and Clinical Implication. Front. Endocrinol. 2021, 12, 585887.
  90. Gruber, T.; Pan, C.; Contreras, R.E.; Wiedemann, T.; Morgan, D.A.; Skowronski, A.A.; Lefort, S.; De Bernardis Murat, C.; Le Thuc, O.; Legutko, B.; et al. Obesity-associated hyperleptinemia alters the gliovascular interface of the hypothalamus to promote hypertension. Cell Metab. 2021, 33, 1155–1170.
  91. Andò, S.; Catalano, S. The multifactorial role of leptin in driving the breast cancer microenvironment. Nat. Rev. Endocrinol. 2012, 8, 263–275.
  92. Ianza, A.; Sirico, M.; Bernocchi, O.; Generali, D. Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer. Front. Cell Dev. Biol. 2021, 9, 641449.
  93. Christopoulos, P.F.; Msaouel, P.; Koutsilieris, M. The role of the insulin-like growth factor-1 system in breast cancer. Mol. Cancer 2015, 14, 43.
  94. Creighton, C.J.; Casa, A.; Lazard, Z.; Huang, S.; Tsimelzon, A.; Hilsenbeck, S.G.; Osborne, C.K.; Lee, A.V. Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2008, 26, 4078–4085.
  95. Pollak, M. Insulin and insulin-like growth factor signalling in neoplasia. Nat. Rev. Cancer 2008, 8, 915–928.
  96. Edakuni, G.; Sasatomi, E.; Satoh, T.; Tokunaga, O.; Miyazaki, K. Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma. Pathol. Int. 2001, 51, 172–178.
  97. Bell, L.N.; Ward, J.L.; Degawa-Yamauchi, M.; Bovenkerk, J.E.; Jones, R.; Cacucci, B.M.; Gupta, C.E.; Sheridan, C.; Sheridan, K.; Shankar, S.S.; et al. Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity. Am. J. Physiol. Endocrinol. Metab. 2006, 291, E843–E848.
  98. Guillaume, V.G.J.; Ruhl, T.; Boos, A.M.; Beier, J.P. The Crosstalk Between Adipose-Derived Stem or Stromal Cells (ASC) and Cancer Cells and ASC-Mediated Effects on Cancer Formation and Progression—ASCs: Safety Hazard or Harmless Source of Tropism? Stem Cells Transl. Med. 2022, 11, 394–406.
  99. Burns, J.S.; Kristiansen, M.; Kristensen, L.P.; Larsen, K.H.; Nielsen, M.O.; Christiansen, H.; Nehlin, J.; Andersen, J.S.; Kassem, M. Decellularized matrix from tumorigenic human mesenchymal stem cells promotes neovascularization with galectin-1 dependent endothelial interaction. PLoS ONE 2011, 6, e21888.
  100. Xu, H.; Li, W.; Luo, S.; Yuan, J.; Hao, L. Adipose derived stem cells promote tumor metastasis in breast Cancer cells by stem cell factor inhibition of miR20b. Cell. Signal. 2019, 62, 109350.
  101. Li, J.J.; Tsang, J.Y.; Tse, G.M. Tumor Microenvironment in Breast Cancer-Updates on Therapeutic Implications and Pathologic Assessment. Cancers 2021, 13, 4233.
  102. Sahai, E.; Astsaturov, I.; Cukierman, E.; DeNardo, D.G.; Egeblad, M.; Evans, R.M.; Fearon, D.; Greten, F.R.; Hingorani, S.R.; Hunter, T.; et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 2020, 20, 174–186.
  103. Gieniec, K.A.; Butler, L.M.; Worthley, D.L.; Woods, S.L. Cancer-associated fibroblasts—Heroes or villains? Br. J. Cancer 2019, 121, 293–302.
  104. Chen, Y.; McAndrews, K.M.; Kalluri, R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat. Rev. Clin. Oncol. 2021, 18, 792–804.
  105. Soundararajan, M.; Kannan, S. Fibroblasts and mesenchymal stem cells: Two sides of the same coin? J. Cell. Physiol. 2018, 233, 9099–9109.
  106. Ugurlu, B.; Karaoz, E. Comparison of similar cells: Mesenchymal stromal cells and fibroblasts. Acta Histochem. 2020, 122, 151634.
  107. Schellenberg, A.; Lin, Q.; Schüler, H.; Koch, C.M.; Joussen, S.; Denecke, B.; Walenda, G.; Pallua, N.; Suschek, C.V.; Zenke, M.; et al. Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks. Aging 2011, 3, 873–888.
  108. Koch, C.M.; Suschek, C.V.; Lin, Q.; Bork, S.; Goergens, M.; Joussen, S.; Pallua, N.; Ho, A.D.; Zenke, M.; Wagner, W. Specific age-associated DNA methylation changes in human dermal fibroblasts. PLoS ONE 2011, 6, e16679.
  109. Liang, W.; Chen, X.; Zhang, S.; Fang, J.; Chen, M.; Xu, Y.; Chen, X. Mesenchymal stem cells as a double-edged sword in tumor growth: Focusing on MSC-derived cytokines. Cell. Mol. Biol. Lett. 2021, 26, 3.
  110. Li, W.; Yang, J.; Zheng, P.; Li, H.; Zhao, S. The Origins and Generation of Cancer-Associated Mesenchymal Stromal Cells: An Innovative Therapeutic Target for Solid Tumors. Front. Oncol. 2021, 11, 723707.
  111. Wu, Q.; Li, B.; Li, Z.; Li, J.; Sun, S.; Sun, S. Cancer-associated adipocytes: Key players in breast cancer progression. J. Hematol. Oncol. 2019, 12, 95.
  112. McLean, K.; Gong, Y.; Choi, Y.; Deng, N.; Yang, K.; Bai, S.; Cabrera, L.; Keller, E.; McCauley, L.; Cho, K.R.; et al. Human ovarian carcinoma–associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J. Clin. Investig. 2011, 121, 3206–3219.
  113. Barcellos-de-Souza, P.; Comito, G.; Pons-Segura, C.; Taddei, M.L.; Gori, V.; Becherucci, V.; Bambi, F.; Margheri, F.; Laurenzana, A.; Del Rosso, M.; et al. Mesenchymal Stem Cells are Recruited and Activated into Carcinoma-Associated Fibroblasts by Prostate Cancer Microenvironment-Derived TGF-β1. Stem Cells 2016, 34, 2536–2547.
  114. Fregni, G.; Quinodoz, M.; Möller, E.; Vuille, J.; Galland, S.; Fusco, C.; Martin, P.; Letovanec, I.; Provero, P.; Rivolta, C.; et al. Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis. EBioMedicine 2018, 29, 128–145.
  115. Li, W.; Zhang, X.; Wu, F.; Zhou, Y.; Bao, Z.; Li, H.; Zheng, P.; Zhao, S. Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in gastric cancer. Cell Death Dis. 2019, 10, 918.
  116. Kamdje, A.H.N.; Etet, P.F.S.; Tagne, R.S.; Vecchio, L.; Lukong, K.E.; Krampera, M. Tumor Microenvironment Uses a Reversible Reprogramming of Mesenchymal Stromal Cells to Mediate Pro-tumorigenic Effects. Front. Cell Dev. Biol. 2020, 8, 545126.
  117. Anvarian, Z.; Mykytyn, K.; Mukhopadhyay, S.; Pedersen, L.B.; Christensen, S.T. Cellular signalling by primary cilia in development, organ function and disease. Nat. Rev. Nephrol. 2019, 15, 199–219.
  118. Peraldi, P.; Ladoux, A.; Giorgetti-Peraldi, S.; Dani, C. The Primary Cilium of Adipose Progenitors Is Necessary for Their Differentiation into Cancer-Associated Fibroblasts that Promote Migration of Breast Cancer Cells In Vitro. Cells 2020, 9, 2251.
  119. Wang, Y.; Liang, Y.; Xu, H.; Zhang, X.; Mao, T.; Cui, J.; Yao, J.; Wang, Y.; Jiao, F.; Xiao, X.; et al. Single-cell analysis of pancreatic ductal adenocarcinoma identifies a novel fibroblast subtype associated with poor prognosis but better immunotherapy response. Cell Discov. 2021, 7, 36.
  120. Dominguez, C.X.; Müller, S.; Keerthivasan, S.; Koeppen, H.; Hung, J.; Gierke, S.; Breart, B.; Foreman, O.; Bainbridge, T.W.; Castiglioni, A.; et al. Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15(+) Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy. Cancer Discov. 2020, 10, 232–253.
  121. Elyada, E.; Bolisetty, M.; Laise, P.; Flynn, W.F.; Courtois, E.T.; Burkhart, R.A.; Teinor, J.A.; Belleau, P.; Biffi, G.; Lucito, M.S.; et al. Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts. Cancer Discov. 2019, 9, 1102–1123.
  122. Costa, A.; Kieffer, Y.; Scholer-Dahirel, A.; Pelon, F.; Bourachot, B.; Cardon, M.; Sirven, P.; Magagna, I.; Fuhrmann, L.; Bernard, C.; et al. Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer. Cancer Cell 2018, 33, 463–479.
  123. Pelon, F.; Bourachot, B.; Kieffer, Y.; Magagna, I.; Mermet-Meillon, F.; Bonnet, I.; Costa, A.; Givel, A.-M.; Attieh, Y.; Barbazan, J.; et al. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat. Commun. 2020, 11, 404.
  124. Sebastian, A.; Hum, N.R.; Martin, K.A.; Gilmore, S.F.; Peran, I.; Byers, S.W.; Wheeler, E.K.; Coleman, M.A.; Loots, G.G. Single-Cell Transcriptomic Analysis of Tumor-Derived Fibroblasts and Normal Tissue-Resident Fibroblasts Reveals Fibroblast Heterogeneity in Breast Cancer. Cancers 2020, 12, 1307.
  125. Bartoschek, M.; Oskolkov, N.; Bocci, M.; Lövrot, J.; Larsson, C.; Sommarin, M.; Madsen, C.D.; Lindgren, D.; Pekar, G.; Karlsson, G.; et al. Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing. Nat. Commun. 2018, 9, 5150.
  126. Zheng, S.; Zou, Y.; Tang, Y.; Yang, A.; Liang, J.-Y.; Wu, L.; Tian, W.; Xiao, W.; Xie, X.; Yang, L.; et al. Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer. OncoImmunology 2022, 11, 2020984.
  127. Chen, Z.; Zhou, L.; Liu, L.; Hou, Y.; Xiong, M.; Yang, Y.; Hu, J.; Chen, K. Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma. Nat. Commun. 2020, 11, 5077.
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