ECM is thin, ~100-nm thick sheets of glycoproteins and proteoglycans. The glycoproteins and proteoglycans are polymers of laminins (LM) and a cross-linked network of collagen IV fibrils [
83]. LM is heterotrimeric (αβγ trimers) glycoprotein (~900 kDa) with 15 different combinations that are derived from five a, three β and three γ subunits, and coded from distinct genes [
84]. In the mammary gland, four distinct LM isoforms [laminin-111 (LM-1; α1, β1, γ1), -322 (LM-5; α3, β3, γ2), -511 (LM-10) and -521 (LM-11)] are present [
85,
86]. Similarly, BM proteoglycans are complex glycosaminoglycans (GAG) chains that vary with developmental stages of the mammary gland [
87]. However, the major component of BM is perlecans. BM interacts with mammary–epithelial cells (MEC) through integrins and transmembrane (TM) proteoglycans, dystroglycan, and syndecan, and is joined to the cytoskeleton for the signaling platform, and controls cell fate [
88,
89]. Epithelial cells receive instructive signals from the ECM through different receptors, including β1-integrin (collagen receptor) and non-integrin receptors discoidin domain receptor 1 (DDR1, recognize multiple ECM proteins) [
90], dystroglycan, and syndecan [
91]. Integrins are TM receptors and are well studied in MEC. Structurally, integrins are composed of 18α and 8β subunits as a heterodimer and form 24 canonical integrin receptors [
92,
93]. These canonical integrin receptors are for collagen (α1β1 and α2β1), LM-111, -511, -521 (α3β1, α6β1, and α6β4), LM-322 (α3β1 and α6β4), MEC fibronectin, and vitronectin (α5β1 and β3 integrins) [
94]. The terms BM and basal lamina have been used interchangeably to refer to the highly specialized ECM, which organizes 20–100 nm thick structure directly underlying the epithelium [
81]. The other major constituents of the basal lamina are LM, collagen IV, nidogens, and perlecan which act as adhesive contacts in epithelial cells. Collagen IV is a heterotrimer formed from six genetically distinct chains. Collagen IV provides an anchor for mammary epithelial cell viability. Nidogen (entactin) is a sulfated glycoprotein (150 kDa), synthesized by fibroblast, and helps in the formation of the basal lamina. Perlecan is a proteoglycan that consists of a core protein (470 kDa) with covalently linked heparin sulfate, a specific class of GAG, and increases the molecular weight of perlecan over 800 kDa [
95]. Perlecan provides instructive cues and is dependent on the context and structural integrity of ECM. Therefore, ECM serves as a major reservoir for GFs and cytokines and alters according to tensional requirements and organization, which change throughout to generate the open architecture of the mammary gland development [
74].