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PMID: 22897853 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Small GTPase R-Ras regulates integrity and functionality of tumor blood vessels.

Cancer cell ·Vol. 22 ·No. 2 ·2012-08-14 ·Pages 235-49

Sawada J, Urakami T, Li F, Urakami A, Zhu W, Fukuda M, Li DY, Ruoslahti E, Komatsu M

Abstract

We show that R-Ras, a small GTPase of the Ras family, is essential for the establishment of mature, functional blood vessels in tumors. The genetic disruption of R-Ras severely impaired the maturation processes of tumor vessels in mice. Conversely, the gain of function of R-Ras improved vessel structure and blood perfusion and blocked plasma leakage by enhanced endothelial barrier function and pericyte association with nascent blood vessels. Thus, R-Ras promotes normalization of the tumor vasculature. These findings identify R-Ras as a critical regulator of vessel integrity and function during tumor vascularization.

MeSH Terms
Adherens Junctions/drug effects,metabolism Animals Antigens, CD/metabolism Basic Helix-Loop-Helix Transcription Factors/metabolism Blood Vessels/abnormalities,growth & development,metabolism,physiopathology Cadherins/metabolism Cell Hypoxia/drug effects Down-Regulation/drug effects Endocytosis/drug effects Endothelial Cells/drug effects,metabolism Humans Hypoxia-Inducible Factor-Proline Dioxygenases Mice Models, Biological Monomeric GTP-Binding Proteins/metabolism Morphogenesis/drug effects Neoplasms/blood supply,metabolism,pathology Neovascularization, Pathologic/metabolism,physiopathology Pericytes/drug effects,metabolism,pathology Phenotype Procollagen-Proline Dioxygenase Regeneration/drug effects Signal Transduction/drug effects Up-Regulation/drug effects Vascular Endothelial Growth Factor A/pharmacology ras Proteins/deficiency,metabolism
Chemicals
Antigens, CD Basic Helix-Loop-Helix Transcription Factors Cadherins Vascular Endothelial Growth Factor A cadherin 5 endothelial PAS domain-containing protein 1 Procollagen-Proline Dioxygenase Egln1 protein, mouse Hypoxia-Inducible Factor-Proline Dioxygenases RRAS protein, human Rras protein, mouse Monomeric GTP-Binding Proteins ras Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sawada Junko
Sanford-Burnham Medical Research Institute at Lake Nona, Orlando, FL 32827, USA.
Urakami Takeo
Li Fangfei
Urakami Akane
Zhu Weiquan
Fukuda Minoru
Li Dean Y
Ruoslahti Erkki
Komatsu Masanobu
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2012.06.013
Published
2012-08-14
Pages
235-49
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC3422514
Subset
IM
Grants
NCI NIH HHS · CA030199 · United States
NCI NIH HHS · P01 CA104898 · United States
NCI NIH HHS · R01 CA125255 · United States
NCI NIH HHS · P30 CA030199 · United States
NCI NIH HHS · CA104898 · United States
NHLBI NIH HHS · R01 HL084516 · United States
NCI NIH HHS · CA125255 · United States
NCI NIH HHS · P30 CA013148 · United States
Corrections
CommentIn
PMID: 22952010
External Links
PubMed source DOI: 10.1016/j.ccr.2012.06.013 PMC Full Text View journal details
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