The Extracellular Matrix in Digestive Cancer

Abstract

The extracellular components of the cancer microenvironment play a critical role in tumor initiation, progression and invasion. In this review we examine the normal formation and function of the basement membrane and extracellular matrix. We characterize the interactions between the matrix and the epithelium and explore the causes and consequences of the extracellular remodeling that accompanies carcinogenesis. Finally, we address the therapeutic possibilities of incorporating matrix as well as epithelial strategies in the management of digestive cancer.

Extracellular Matrix and Colorectal Cancer: How Surrounding Microenvironment Affects Cancer Cell Behavior?

“…The BM proteins are synthesized by both the epithelial and the mesenchymal cells under physiological conditions (Simon‐Assmann et al, , ) and rearranged to a characteristic sheet‐like structure of 100–300 nm of thickness. The main constituent of BM is the Collagen IV, a network‐forming collagen composed by a trimerization of alpha chains (two α1‐ and one α2‐chain) encoded by six genes ( COL4A1 ‐ COL4A6 ) and other proteins such as the proteoglycan perlecan and the glycoproteins laminin, fibronectin, and nidogen (Worthley et al, ). From a structural point of view, the stromal ECM is constituted by similar components already present in the BM, but Collagen IV is substituted by Collagen I ( COL1A1 , COL1A2 ), this last forming a 3D structure thanks to its fibrillar proprieties.…”

Solubilized extracellular matrix from brain and urinary bladder elicits distinct functional and phenotypic responses in macrophages

“…); brain ECM (B-ECM) is deficient in these components but enriched with proteoglycans such as myelins, leticans, and chondroitin sulfate [12,33e35]. Both B-ECM and U-ECM contain glycosaminoglycans (GAGs) such as hyaluronic acid (HA) and sulfated GAGs [12]; however, the types of GAGs, the matricellular proteins they interact with, the molecular weight of the GAGs, and molecular interactions GAGs utilize to help orchestrate ECM assembly and cell behavior are unique in both B-ECM and U-ECM [34,35]. Given that proteoglycans, GAGs, and their degradation products are all capable of influencing macrophage phenotype and function [36e38], it is reasonable to speculate that the macrophage phenotype initiated by B-ECM could be distinct from the phenotype initiated by U-ECM.…”

Mining Pathway Associations from Networks of Mutual Exclusivity Interactions

“…FA provides mechanical linkage to ECM, and as a biochemical signaling hub to concentrate and direct numerous signaling proteins at sites of integrin binding and clustering [50]. Concurrently FA, ECM and adheren junctions actively contribute to the normal development, maintenance of the gastrointestinal tract and play important roles in stomach cancer [52] and all three pathways are mined by our algorithm.…”