Apelin-driven Endothelial Cell Migration Sustains Intestinal Progenitor Cells and Tumor Growth

Overview

Journal Nat Cardiovasc Res

Publisher Springer Nature

Specialty Cardiology & Vascular Diseases

Date 2022 May 23

PMID 35602406

Authors

Jeremiah Bernier-Latmani

Christophe Cisarovsky

Samantha Mahfoud

Simone Ragusa

Isabelle Dupanloup

David Barras

Francois Renevey

Sina Nassiri

Pascale Anderle

Mario Leonardo Squadrito

Stefanie Siegert

Suzel Davanture

Alejandra Gonzalez-Loyola

Nadine Fournier

Sanjiv A Luther

Rui Benedito

Philippe Valet

Bin Zhou

Michele de Palma

Mauro Delorenzi

Christine Sempoux

Tatiana V Petrova

Affiliations

Soon will be listed here.

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.

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