Small GTPase R-Ras Regulates Integrity and Functionality of Tumor Blood Vessels

SummaryWe 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.

Graphical AbstractFigure optionsDownload high-quality image (269 K)Download as PowerPoint slideHighlights
► Normalization of pathologically regenerating vasculature by a Ras homolog
► A crucial role of R-Ras for endothelial integrity
► R-Ras regulates pericytes and their association with tumor vessels
► A potential O2-sensing independent vascular normalization phenomenon identified