Figure 4.

HGF signals via c-MET to activate satellite cell proliferation and increase the penetrance of injection-site tumor formation. A) P7KP mice were treated with IP tamoxifen and IM saline or 50 ng hepatocyte growth factor (HGF) in a total volume of 25 μl. The mice were treated with EdU prior to euthanasia, and the number of Pax7/EdU double positive cells was determined via immunofluorescence. A greater number of proliferating cells was seen in the P7KP mice treated with IM HGF. B) P7KP mice were treated with tamoxifen on Day 0 along with a concurrent IM injection into the gastrocnemius muscle with IM saline, cardiotoxin, or HGF. C,D) All mice treated with IM cardiotoxin (14/14) developed a sarcoma with rapid kinetics at the injection site. A minority of mice treated with IM saline (3/12) developed an injection-site sarcoma with slower kinetics. When mice were treated with IM HGF, the majority (11/13) developed an injection-site sarcoma with similar kinetics to IM saline. E) P7KP; c-Met^flox/+ and P7KP; c-Met^flox/flox mice were treated with IP tamoxifen and IM HGF and evaluated for sarcoma formation at the IM injection site. F,G) The increased penetrance of injection-site sarcomas observed following treatment with IP tamoxifen and IM HGF in P7KP mice is dependent on signaling through c-MET. * (p<0.05), ** (p<0.01), *** (p<0.001), **** (p<0.0001).