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. 2020 Dec 7;9(12):2629. doi: 10.3390/cells9122629

Figure 2.

Figure 2

(A,B) Extracellular matrix (ECM) and epithelial cell phenotype regulation under physiological context. Colonic epithelial cells interact with the basement membrane (BM) composed of collagen type IV (COLL IV), fibronectin (FN), several proteoglycan (PG) and laminin (LN) subtypes. The BM allows epithelial cell migration from proliferating to differentiating compartments along the crypt axis. Different LN isoforms are expressed in these two compartments: LN211 is expressed at the crypt bottom near the proliferative cells (ISC and TA cells), whereas LN111 and LN511 are mainly found within the differentiation compartment. The differentiated cells sense ECM components with different integrin (ITG) isoforms. (C,D) Extracellular matrix (ECM) and altered epithelium contexts. In the aberrant crypt or during inflammatory bowel disease (IBD) and colorectal cancer (CRC), the epithelium displays several alterations, like a tissue architecture deformation (i.e., crypt fission or distortion), and increases the ECM rigidity support (inflammation and cancer). In fact, the ECM network undergoes high remodeling during pathology compared to physiology: (i) increased fibrillar collagen deposition (COLL I and III) and crosslinking via lysyl oxidase enzymes (LOX) that modify colonic tissue stiffness and (ii) basement membrane disruption and ECM free fragments releasing due to metalloproteinase degradation (MMP, like MMP2 and MMP9). ECM processing affects epithelial cell behaviors like proliferation, stemness, epithelia-mesenchymal transition (EMT) or survival, contributing to disease progression and favoring cancer-initiating cell (CIC) phenotypes.