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 assessed the lymphatic vasculature in this context. The analyses revealed that both E1−/− and E1-E933A mice displayed a higher density of LYVE-1 positive vessels; however, their functionality was severely compromised after colitis induction. Taken together, these results suggest that the loss of EMILIN-1 expression may cause the reduction of the inflammatory resolution during colon cancer progression due to a decreased lymph flow and impaired inflammatory cell drainage.
Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis / A. Capuano, E. Pivetta, G. Sartori, G. Bosisio, A. Favero, E. Cover, E. Andreuzzi, A. Colombatti, R. Cannizzaro, E. Scanziani, L. Minoli, F. Bucciotti, A.I. Amor Lopez, K. Gaspardo, R. Doliana, M. Mongiat, P. Spessotto. - In: MATRIX BIOLOGY. - ISSN 0945-053X. - 83(2019), pp. 97-115.
|Titolo:||Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis|
|Parole Chiave:||Colitis-associated cancer; Extracellular matrix; Lymphatic aberrations|
|Settore Scientifico Disciplinare:||Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria|
|Data di pubblicazione:||2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.matbio.2019.08.006|
|Appare nelle tipologie:||01 - Articolo su periodico|