Suppression of tumor angiogenesis by Gα13 haploinsufficiency

Abstract

Heterotrimeric G proteins are critical transducers of cellular signaling. Of the four families of G proteins, the physiological function of Gα13 is less well understood. Gα 13 gene-deleted mice die at embryonic day ∼9.5. Here, we show that heterozygous Gα13+/- mice display defects in adult angiogenesis. Female Gα13+/- mice showed a higher number of immature follicles and a lower density of blood vessels in the mature corpus luteum compared with Gα13+/+ mice. Furthermore, implanted tumors grew slower in Gα13+/- host mice. These tumor tissues had many fewer blood vessels compared with those from Gα13+/+ host mice. Moreover, bone marrow-derived progenitor cells from Gα 13+/+ mice rescued the failed growth of allografted tumors when reconstituted into irradiated Gα 13+/- mice. Hence, Gα13 is haploinsufficient for adult angiogenesis in both the female reproductive system and tumor angiogenesis. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.