Abrogation of EMILIN1- β1 integrin interaction promotes experimental colitis and colon carcinogenesis.

Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis. Matrix Biol. 2019 Aug 31;: Authors: Capuano A, Pivetta E, Sartori G, Bosisio G, Favero A, Cover E, Andreuzzi E, Colombatti A, Cannizzaro R, Scanziani E, Minoli L, Bucciotti F, Lopez AIA, Gaspardo K, Doliana R, Mongiat M, Spessotto P Abstract Colon cancer is one of the first tumor types where a functional link between inflammation and tumor onset has been described; however, the microenvironmental cues affecting colon cancer progression are poorly understood. Here we demonstrate that the expression of the ECM molecule EMILIN-1 halts the development of AOM-DSS induced tumors. In fact, upon AOM-DSS treatment the Emilin1-/- (E1-/-) mice were characterized by a higher tumor incidence, bigger adenomas and less survival. Similar results were obtained with the E933A EMILIN-1 (E1-E933A) transgenic mouse model, expressing a mutant EMILIN-1 unable to interact with α4/α9β1 integrins. Interestingly, upon chronic treatment with DSS, E1-/- and E1-E933A mice were characterized by the presence of increased inflammatory infiltrates, higher colitis scores and more severe mucosal injury respect to the wild type (E1+/+) mice. Since alterations of the intestinal lymphatic network are a well-established feature of human inflammatory bowel disease and EMILIN-1 is a key structural element in the maintenance of the integrity of lymphatic vessels, we asses...
Source: Matrix Biology - Category: Molecular Biology Authors: Tags: Matrix Biol Source Type: research