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1 Fusion of tumor cells and macrophages are relevant for cancer progression and should be further explored as potential targets for immunotherapies in precision medicine + 589 word(s) 589 2020-03-20 10:52:08 |
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Kaifi, J. Tumor Cells with Macrophages. Encyclopedia. Available online: https://encyclopedia.pub/entry/442 (accessed on 29 March 2024).
Kaifi J. Tumor Cells with Macrophages. Encyclopedia. Available at: https://encyclopedia.pub/entry/442. Accessed March 29, 2024.
Kaifi, Jussuf. "Tumor Cells with Macrophages" Encyclopedia, https://encyclopedia.pub/entry/442 (accessed March 29, 2024).
Kaifi, J. (2020, March 20). Tumor Cells with Macrophages. In Encyclopedia. https://encyclopedia.pub/entry/442
Kaifi, Jussuf. "Tumor Cells with Macrophages." Encyclopedia. Web. 20 March, 2020.
Tumor Cells with Macrophages
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The biological nature of the various populations of circulating tumor cells (CTCs) within the blood is still not well understood. Tumor cell fusion with immune cells is a longstanding hypothesis that has caught more attention in recent times. Specifically, fusion of tumor cells with macrophages might lead to the development of metastasis by acquiring features such as genetic and epigenetic heterogeneity, chemotherapeutic resistance, and immune tolerance. A unique circulating cell population has been identified as being potential fusions cells, characterized by distinct, large, polymorphonuclear cancer-associated cells with a dual epithelial and macrophage phenotype. Artificial fusion of tumor cells with macrophages leads to migratory, invasive, and metastatic phenotypes. Further studies might investigate whether these have a potential impact on the immune response towards the cancer. Such fusion cells could be a key component in cancer metastasis, and therefore, evolve as a diagnostic and therapeutic target in cancer precision medicine.

Cancer tumor fusion cells macrophages liquid biomarkers circulating tumor cells

1. Introduction

Recent reports on circulating cancer-associated cells with both epithelial and macrophage/myeloid phenotypes in cancer patients, combined with genetic evidence, have supported the idea that fusion has a critical role in cancer progression (Figure 1)[1][2][3][4].

2. Fusion of Tumor Cells with Macrophages

Macrophage M1 or M2 polarization appears to be critical for various aspects of immune responses to cancer and its progression[5]. Macrophage infiltration of the primary tumor and polarization depend on cytokines in the tumor microenvironment (TME)[6]. Within the TME, tumor-associated macrophage polarization to the M1 phenotype can be triggered through bacterial lipopolysaccharide (LPS) and by T helper 1 (Th1) cytokines, such as IFN-γ and also by TNF-α[7]. The M1 phenotype is associated with anti-tumor properties[8]. M2 phenotype macrophages have pro-tumoral effects, leading to increased cancer cell survival, proliferation, invasiveness, and immunosuppression in favor of the tumor[5]. M2 polarization is induced by T helper 2 cytokines interleukin (IL)-4, IL-13, macrophage colony-stimulating factor (M-CSF), and transforming growth factor (TGF)-β[8]. M2 macrophages are anti-inflammatory, immunosuppressive, and promote cancer progression, chemoresistance, and metastasis[9][10]. M2 macrophages have critical interactions with tumor cells, but also with cells associated with tumor progression, such as Th2 cells, cancer-associated fibroblasts, regulatory T cells (Tregs), and myeloid-derived suppressor cells[5]. M2 polarization phenotypes have also been observed in tumor fusion cells[11]. Importantly, macrophages also have a high fusogenic potential, which is also likely to occur with tumor cells[12][13][8][14]. In vitro and in vivo studies suggest that metastatic cells can be the result of the fusion of tumor cells with cells of hematopoietic/myeloid lineage, specifically with macrophages[15][12][16][13][17][18][19][20] . Importantly, patient-derived tumor-macrophage fusion cells were shown to have M2 macrophage phenotypes[17][18] . In a murine melanoma metastasis model, certain clones of lung metastasis cells had properties of melanoma cell—macrophage fusion cells[21]. Importantly, fusion of tumor cells with macrophages is supported through the observation of these fusion cells in cancer patients[17][18][22][23] . Macrophage fusion receptor DAP12 expression is associated with higher metastatic rates in breast cancer patients[13][24][25] . It remains unclear whether tumor-associated macrophages fuse within the tumor microenvironment at the site of the tumor, in the blood, or in the lymphatic system. Understanding molecular fusion mechanisms between macrophages and tumor cells and the impact that fusion cells have on the immune system is of high interest in identifying therapeutic targets.

Ijms 21 01872 g001 550

Figure 1. Concepts of fusion between tumor cells and macrophages. It is hypothesized that tumor-associated M2-polarized macrophages (TAMs) fuse their membranes with tumor cells, forming a tumor–macrophage hybrid cell. These fusion cells are large, mononuclear/polynuclear, and express both epithelial and myeloid markers. Importantly, fusion cells exert pro-tumorigenic and pro-metastatic effects through the outlined mechanisms.

References

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  4. Germana Rappa; Javier Mercapide; Aurelio Lorico; Spontaneous Formation of Tumorigenic Hybrids between Breast Cancer and Multipotent Stromal Cells Is a Source of Tumor Heterogeneity. The American Journal of Pathology 2012, 180, 2504-2515, 10.1016/j.ajpath.2012.02.020.
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  12. Greggory S. Laberge; Eric Duvall; Zachary Grasmick; Kay Haedicke; John M Pawelek; A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis. PLoS ONE 2017, 12, e0168581, 10.1371/journal.pone.0168581.
  13. Ivan Shabo; Kristine Midtbö; Henrik Andersson; Emma Åkerlund; Hans Olsson; Pia Wegman; Cecilia Gunnarsson; Annelie Lindström; Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction. BMC Cancer 2015, 15, 1-11, 10.1186/s12885-015-1935-0.
  14. Elizabeth H. Chen; Eric N. Olson; Unveiling the Mechanisms of Cell-Cell Fusion. Science 2005, 308, 369-373, 10.1126/science.1104799.
  15. Rossitza Lazova; Greggory S. Laberge; Eric Duvall; Nicole Spoelstra; Vincent Klump; Mario Sznol; Dennis Cooper; Richard A. Spritz; Joseph T. Chang; John M. Pawelek; et al. A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer. PLOS ONE 2013, 8, e66731, 10.1371/journal.pone.0066731.
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  18. Clawson, G.A.; Matters, G.L.; Xin, P.; Imamura-Kawasawa, Y.; Du, Z.; Thiboutot, D.M.; Helm, K.F.; Neves, R.I.; Abraham, T. Macrophage-tumor cell fusions from peripheral blood of melanoma patients. PLoS ONE 2015, 10, e0134320.
  19. John M Pawelek; Cancer cell fusion with migratory bone marrow-derived cells as an explanation for metastasis: new therapeutic paradigms. Future Oncology 2008, 4, 449-452, 10.2217/14796694.4.4.449.
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  23. Kaifi, J.T.; Kunkel, M.; Das, A.; Harouaka, R.A.; Dicker, D.T.; Li, G.; Zhu, J.; Clawson, G.A.; Yang, Z.; Reed, M.F.; et al. Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: A prospective trial with different detection techniques. Cancer Biol. Ther. 2015, 16, 699–708.
  24. Shabo, I.; Olsson, H.; Stal, O.; Svanvik, J. Breast cancer expression of DAP12 is associated with skeletal and liver metastases and poor survival. Clin. Breast Cancer 2013, 13, 371–377.
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