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Modulation of G Protein Signaling Normalizes Tumor Vessels

Western Australian Institute for Medical Research, The University of Western Australia Centre for Medical Research, Perth, Western Australia, Australia

Requests for reprints: Ruth Ganss, Western Australian Institute for Medical Research, Rear 50 Murray Street, MRF Building, Level 5, Perth, Western Australia 6000, Australia. Phone: 61-8-9224-0354; Fax: 61-8-9224-0332; E-mail: ganss{at}waimr.uwa.edu.au.

Key Words: Regulator of G protein signaling 5 • angiogenesis • vessel normalization • immunotherapy

G protein–coupled biological processes are important for an ever-increasing number of human diseases and require fine-tuning through accessory molecules such as the regulators of G protein signaling (RGS). RGS5, a marker for tumor-resident pericytes, was recently established as playing a pivotal role in vascular maturation and vessel remodeling during carcinogenesis. Remarkably, tumors arising in a RGS5-deficient background display vessels with normalized morphology and an overall improved blood flow. Furthermore, these morphologic changes also lead to dramatic improvements in lymphocyte access to tumors and success of antitumor immunotherapy. Here, we consider the implications of these findings, and how they contribute to enhancing our understanding of remodeling angiogenic vessels as means for improving anticancer therapies. [Cancer Res 2009;69(2):396–9]