Description
Hepatocyte growth factor (HGF) and its receptor, c-Met, play a role in lung tumor development and progression. Extent of expression of both HGF and c-Met have been shown to be negative prognostic indicators of survival and recurrence in non-small cell lung cancer. To further define a role for HGF in lung cancer development and growth, investigators have generated transgenic mice that overexpress HGF in the airway epithelium. The HGF transgene was verified to be expressed only in the lungs of transgenic mice. The transgenic mouse lung histology exhibited congestion in the alveolar spaces, excess production of blood vessels and a convoluted pattern of airways with wide bifurcations. The number of lung tumors from tobacco-carcinogen treated transgenic animals versus the number of lung tumors from tobacco carcinogen treated wild-type animals was significantly higher. The percent of animals with tumors was 75% in the transgenic group compared to 48.8% in the wild-type group. The main effect was an increase in tumor multiplicity; average size of tumors was not different between groups. Additionally, the tumors that arose in the transgenic mice contained increased HGF protein compared to tumors from the wild-type mice. These results indicate that lung carcinogenesis induced by a tobacco carcinogen is enhanced by expression of the HGF transgene. This model recapitulates the phenotype of aggressive lung adenocarcinoma that overexpress HGF and will be useful in evaluating anti-tumor agents that target either the HGF/c-Met pathway or downstream effects such as angiogenesis or invasion.IP Status
Research Tool
