Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/68399
Title: Inhibition of the p110α isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis
Author: Soler, Adriana
Serra, Helena
Pearce, Wayne
Angulo Aguado, Ana
Guillermet-Guibert, Julie
Friedman, Lori S.
Viñals Canals, Francesc
Gerhardt, Holger
Casanovas i Casanovas, Oriol
Graupera, Mariona
Vanhaesebroeck, Bart
Issue Date: 16-Sep-2013
Publisher: Rockefeller University Press
Abstract: Understanding the direct, tumor cell<br>intrinsic effects of PI 3-kinase (PI3K) has been a key focus of research to date. Here, we report that cancer cell<br>extrinsic PI3K activity, mediated by the p110α isoform of PI3K, contributes in an unexpected way to tumor angiogenesis. In syngeneic mouse models, inactivation of stromal p110α led to increased vascular density, reduced vessel size, and altered pericyte coverage. This increased vascularity lacked functionality, correlating with enhanced tumor hypoxia and necrosis, and reduced tumor growth. The role of p110α in tumor angiogenesis is multifactorial, and includes regulation of proliferation and DLL4 expression in endothelial cells. p110α in the tumor stroma is thus a regulator of vessel formation, with p110α inactivation giving rise to nonfunctional angiogenesis, which can stunt tumor growth. This type of vascular aberration differs from vascular endothelial growth factor<br>centered antiangiogenesis therapies, which mainly lead to vascular pruning. Inhibition of p110α may thus offer a new antiangiogenic therapeutic opportunity in cancer.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1084/jem.20121571
It is part of: Journal of Experimental Medicine, 2013, vol. 210, num. 10, p. 1937-1945
Related resource: http://dx.doi.org/10.1084/jem.20121571
URI: http://hdl.handle.net/2445/68399
ISSN: 0022-1007
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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