The Role of Extracellular Matrix Proteins in Breast Cancer

Abstract

The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell–cell and cell–matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors’ action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.

The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment

“…Integrin β1 is also involved in in control of the ECM and epithelial differentiation as shown through the effect of the absence of integrin β1 impairing STAT5 signaling, causing epithelial cells to detach from the basement membrane [ 145 ]. In addition, laminin is also involved in organogenesis and early development processes, likely due to their interactions on the cell surface [ 145 ].…”

SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways

“…We also observed down-regulation of FN1 transcript (−3.1 f.ch. ), which encodes preprotein fibronectin, a proteolytically processed glycoprotein involved in cell adhesion and migration processes, wound healing, and metastasis [ 32 ]. Cell cycle regulator CCND1 (cyclin D1) was also down-regulated (−3.2 f.ch.)…”

Notch Signaling in Breast Tumor Microenvironment as Mediator of Drug Resistance

“…In a follow-up study, the Notch-regulated uPA–plasmin axis activates latent TGF-β in stroma cells [ 106 , 107 ], which stimulates the TGF-β receptor 1, another Notch target gene in BCs [ 95 ]. Several reports have recently revealed that the ECM proteins Periostin and Tenascin C play key roles as metastasis niche components for tumor-initiating cells that invade different organs [ 108 , 109 ]. By enhancing Wnt and Notch signaling in cancer cells, these proteins provide physical as well as signaling support for metastasis-initiating cells [ 110 ].…”