2026-07-23T19:37:08Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/157522024-09-27T09:15:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Bernier-Latmani, Jeremiah
author
Cisarovsky, Christophe
author
Mahfoud, Samantha
author
Ragusa, Simone
author
Dupanloup, Isabelle
author
Barras, David
author
Renevey, François
author
Nassiri, Sina
author
Anderle, Pascale
author
Squadrito, Mario Leonardo
author
Siegert, Stefanie
author
Davanture, Suzel
author
González-Loyola, Alejandra
author
Fournier, Nadine
author
Luther, Sanjiv A
author
Benedito, Rui
author
Valet, Philippe
author
Zhou, Bin
author
De Palma, Michele
author
Delorenzi, Mauro
author
Sempoux, Christine
author
Petrova, Tatiana V
funder
Swiss National Science Foundation
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2023-04-11T10:20:12Z
2023-04-11T10:20:12Z
2022-05
Nat Cardiovasc Res. 2022 May;1(5):476-490
10.1038/s44161-022-00061-5
2731-0590
Nature cardiovascular research
35602406
http://hdl.handle.net/20.500.12105/15752
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.
eng
Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth.
journal article
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Apelin_driven endothelial cell Nat Cardiovasc Res 2022.pdf
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https://repisalud.isciii.es/bitstreams/974bc0c3-836d-488c-b375-7d26a23ac323/download
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Apelin_driven endothelial cell Nat Cardiovasc Res 2022.pdf.txt