Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization.
We identified regulator of G-protein signaling-5 (RGS-5) as an angiogenic pericyte marker at sites of physiologic and pathologic angiogenesis. In a mouse model of pancreatic islet cell carcinogenesis, RGS-5 is specifically induced in the vasculature of premalignant lesions during the "angiogenic switch" and further elevated in tumor vessels. Similarly, RGS-5 is overexpressed in highly angiogenic astrocytomas but not in hypoxia-inducible factor-1alpha (HIF-1alpha)-deficient tumors, which grow along preexisting brain capillaries without inducing neovessels. Elevated levels of RGS-5 in pericytes are also observed during wound healing and ovulation indicating a strong correlation between RGS-5 expression and active vessel remodeling beyond tumor angiogenesis. Moreover, antitumor therapy, which reverses tumor vasculature to an almost normal morphology, results in down-regulation of RGS-5 transcription. Taken together, these data demonstrate for the first time a factor that is specific for "activated" pericytes. This further supports the notion that pericytes, like endothelial cells, undergo molecular changes during neovascularization that makes them a novel target for antiangiogenic therapy.
Department of Molecular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Mario
M
Berger
Gabriele
G
Bergers
Bernd
B
Arnold
Günter J
GJ
Hämmerling
Ruth
R
Ganss
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007515:Islets of Langerhans / Q000098:blood supply; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D010060:Ovulation; D020286:Pericytes / Q000502:physiology*; D016133:Polymerase Chain Reaction; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D017931:DNA Primers; D020710:RGS Proteins; C491349:RGS5 protein, human