Hepatocyte growth factor promotes tumor growth in a novel in vivo model ofhuman lung cancer

Significant progress has been made toward identifying growth factors that d isplay autocrine or paracrine effects on the growth of lung cancer cells. D etermining the in vivo relevance of specific growth factors on lung tumor f ormation, however, has not often been demonstrated in laboratory models. Al though hepatocyte growth factor (HGF) has been shown to have mitogenic and motogenic effects on human lung cancer cells in vitro, and to have prognost ic importance in patients with lung cancer, the effects of HGF on tumor beh avior in vivo remain unknown. We therefore developed an airway tumor xenogr aft model that allowed us to test the hypothesis that HGF promotes human no n-small cell lung cancer (NSCLC) growth in vivo. Human airway tumor xenogra fts were created in Severe Combined Immunodeficient mice by injecting human lung adenocarcinoma cells into human bronchial segments. After determining the optimal times for tumor-cell injection and the time course of tumor gr owth, we evaluated the effects of HGF on tumor growth by injecting recombin ant HGF, or saline as a control, into the lumen of tumor xenografts for 10 consecutive days. Histologic evaluation 2 to 3 wk later revealed that the H GF-injected xenografts had a significantly greater tumor volume and more tu mor cells were located in the submucosal space than were found in the salin e-injected xenografts. These data demonstrate the usefulness of this novel in vivo model to study NSCLC, and show that HGF promotes both the growth an d invasion of human lung cancer in vivo.