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Article Dans Une Revue Nature Cardiovascular Research Année : 2022

Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth

Stefanie Siegert
  • Fonction : Auteur
Nadine Fournier
Sanjiv Luther
  • Fonction : Auteur
Rui Benedito
Bin Zhou
Michele de Palma
Mauro Delorenzi
Christine Sempoux
  • Fonction : Auteur
Tatiana Petrova

Résumé

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.

Dates et versions

hal-04570990 , version 1 (07-05-2024)

Identifiants

Citer

Jeremiah Bernier-Latmani, Christophe Cisarovsky, Samantha Mahfoud, Simone Ragusa, Isabelle Dupanloup, et al.. Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth. Nature Cardiovascular Research, 2022, 1 (5), pp.476-490. ⟨10.1038/s44161-022-00061-5⟩. ⟨hal-04570990⟩
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