Suppression of Tumor Angiogenesis by Gα13 Haploinsufficiency

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