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 a4/a9b1 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 (E1þ/þ) 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.
