Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth.
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State: Public
Version: Final published version
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State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_998EFE1BCFC2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth.
Journal
Nature cardiovascular research
ISSN
2731-0590 (Electronic)
ISSN-L
2731-0590
Publication state
Published
Issued date
05/2022
Peer-reviewed
Oui
Volume
1
Number
5
Pages
476-490
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Pubmed
Create date
24/05/2022 12:15
Last modification date
12/08/2023 6:13