| First Author | Capuano A | Year | 2019 |
| Journal | Matrix Biol | Volume | 83 |
| Pages | 97-115 | PubMed ID | 31479698 |
| Mgi Jnum | J:285591 | Mgi Id | MGI:6391916 |
| Doi | 10.1016/j.matbio.2019.08.006 | Citation | Capuano A, et al. (2019) Abrogation of EMILIN1-beta1 integrin interaction promotes experimental colitis and colon carcinogenesis. Matrix Biol 83:97-115 |
| abstractText | 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 alpha4/alpha9beta1 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. |
