Suppression of tumor angiogenesis by Galpha(13) haploinsufficiency.
Heterotrimeric G proteins are critical transducers of cellular signaling. Of the four families of G proteins, the physiological function of Galpha(13) is less well understood. Galpha(13) gene-deleted mice die at embryonic day approximately 9.5. Here, we show that heterozygous Galpha(13)(+/-) mice display defects in adult angiogenesis. Female Galpha(13)(+/-) mice showed a higher number of immature follicles and a lower density of blood vessels in the mature corpus luteum compared with Galpha(13)(+/+) mice. Furthermore, implanted tumors grew slower in Galpha(13)(+/-) host mice. These tumor tissues had many fewer blood vessels compared with those from Galpha(13)(+/+) host mice. Moreover, bone marrow-derived progenitor cells from Galpha(13)(+/+) mice rescued the failed growth of allografted tumors when reconstituted into irradiated Galpha(13)(+/-) mice. Hence, Galpha(13) is haploinsufficient for adult angiogenesis in both the female reproductive system and tumor angiogenesis.
Chen
Lin
L
Department of Physiology, Weill Medical College of Cornell University, New York, New York 10065, USA.
Zhang
J Jillian
JJ
Rafii
Shahin
S
Huang
Xin-Yun
XY
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001853:Bone Marrow; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003338:Corpus Luteum / Q000098:blood supply; D015536:Down-Regulation; D055808:Drug Discovery; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D051379:Mice; D009154:Mutation; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics*; D006080:Ovarian Follicle / Q000098:blood supply; D034622:RNA Interference; D012098:Reproduction / Q000235:genetics / Q000502:physiology; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D044365:GTP-Binding Protein alpha Subunits, G12-G13