Role of Hepatocyte Growth Factor Autocrine Loop in Growth and Metastasis of Breast Cancer

摘要

We previously demonstrated elevated HGF and Met expression in regions of invasive human breast carcinomas, suggesting a role of autocrine HGF loops in invasive breast cancer. As a first step to validate this hypothesis, we have now demonstrated that: (a) elevated HGF and Met expression occurs in some newly- derived breast and non-small cell lung carcinoma cell lines; and (b) several carcinoma cell lines showed autocrine tyrosine-phosphorylation of Met and increased cell survival, consistent with the presence of autocrine HGF loops. Thus, we have identified autocrine HGF loops in newly-derived breast carcinoma and NSCLC cell lines, and have correlated the activation of HGF autocrine loops with cell survival. The next stage of this study is to design peptide antagonists of HGF that block HGF ligand receptor binding, and to test the efficacy of these antagonists in inhibiting tumorigenic functions. This information will be important in the search for novel targets for therapeutic intervention in breast cancer.