Figure 1.
Platelet G proteins and growth of orthotopic ovarian cancer tumors in mice and viability of cancer cells. (A) Gi△/△ mice (left panel) and G13△/△ mice (middle panel) developed smaller tumors 6 to 8 weeks after intraperitoneal injection of ID8 murine ovarian cancer cells (Gi△/△, 0.54 ± 0.1 g; Gifl/fl, 1.46 ± 0.1 g; G13△/△, 0.17 ± 0.007 g; G13fl/fl, 0.42 ± 0.065 g). The deficiency of Gq protein in platelets (Gq△/△) did not affect the final tumor size in mice (Gq△/△, 0.41 ± 0.07 g; Gqfl/fl, 0.48 ± 0.11 g) (right panel). n = 6 to 8 mice per group. (B) The proliferation rate of cancer cells inside tumor nodules was quantified by the percentage of Ki67 positivity per high-power field (HPF): Gifl/fl, 45 ± 4%; Gi△/△, 24 ± 5%; G13fl/fl, 39 ± 5%; G13△/△, 16 ± 2%; Gqfl/fl, 42 ± 2%; Gq△/△, 43 ± 3%). Three tumor-bearing mice, 1 nodule from the mouse, and 3 or 4 HPFs per nodule were examined. (C) Invasiveness of cancer cells after incubation with G protein–deficient platelets was measured in vitro by migration assay: Gifl/fl: 65 ± 6 per HPF; Gi△/△, 34 ± 4 per HPF; G13fl/fl, 65 ± 7 per HPF; G13△/△, 33 ± 5 per HPF; Gqfl/fl, 54 ± 4 per HPF; Gq△/△, 54 ± 7 per HPF. Four HPFs from 3 membranes were imaged and analyzed. All data are mean ± standard deviation. A 2-tailed Student t test was used to determine statistical significance; P < .05 was considered significant.