| Literature DB >> 35602406 |
Jeremiah Bernier-Latmani1, Christophe Cisarovsky1, Samantha Mahfoud1, Simone Ragusa1, Isabelle Dupanloup2, David Barras1,2, François Renevey3, Sina Nassiri4,2, Pascale Anderle2, Mario Leonardo Squadrito4, Stefanie Siegert3, Suzel Davanture1, Alejandra González-Loyola1, Nadine Fournier2, Sanjiv A Luther3, Rui Benedito5, Philippe Valet6, Bin Zhou7, Michele De Palma4, Mauro Delorenzi1,2, Christine Sempoux8, Tatiana V Petrova1,4.
Abstract
Stem and progenitor cells residing in the intestinal crypts drive the majority of colorectal cancers (CRCs), yet vascular contribution to this niche remains largely unexplored. VEGFA is a key driver of physiological and tumor angiogenesis. Accordingly, current anti-angiogenic cancer therapies target the VEGFA pathway. Here we report that in CRC expansion of the stem/progenitor pool in intestinal crypts requires VEGFA-independent growth and remodeling of blood vessels. Epithelial transformation induced expression of the endothelial peptide apelin, directs migration of distant venous endothelial cells towards progenitor niche vessels ensuring optimal perfusion. In the absence of apelin, loss of injury-inducible PROX1+ epithelial progenitors inhibited both incipient and advanced intestinal tumor growth. Our results establish fundamental principles for the reciprocal communication between vasculature and the intestinal progenitor niche and provide a mechanism for resistance to VEGFA-targeting drugs in CRCs.Entities:
Year: 2022 PMID： 35602406 PMCID： PMC7612746 DOI： 10.1038/s44161-022-00061-5
Source DB: PubMed Journal: Nat Cardiovasc Res ISSN： 2731-0590