肺癌多臓器転移モデルによる転移の分子機構解明と治療への応用

Lung cancer is a leading cause of malignancy-related death worldwide, and over 90% of deaths from lung cancer can be attributed to metastases. To explore molecular pathogenesis of lung cancer, we recently established multiple-organ metastasis models of human lung cancer cells in SCID mice depleted of NK cells. The pattern of metastasis in our models is similar with that observed in lung cancer patients. Using our models, we have shown that overexpression of cytokines, such as macrophage colony-stimulating factor and interleukin-10, resulted in organ-specific inhibition of metastasis by human lung cancer cell lines, suggesting differential regulation of metastasis by organ microenvironment. We further demonstrated that expression of human cancer cells were heterogenous, and that anti-metastastic effect of MMP inhibitor, a molecular targeted drug, could be organ specific, consistent with the results in recent clinical trials. Further intensive analyses using clinically relevant metastasis models (e.g., multiple-organ metastasis models) are warranted for establishment of novel, effective treatment for lung cancer metastasis.