Novel strategies against metastasis are urgently needed to improve lung cancer treatment. However, the molecular mechanism of metastasis of lung cancer, which is important for the development of the effective treatment, remains largely to be elucidated. For further studies of lung cancer metastasis, we are trying to develop a novel orthotopic transplantation model in the mouse.
We established GFP-labeled clones from human lung cancer cell lines and transplanted them orthotopically into the lung of Balb/c nude mice with matrigel. Tumor formation at the orthotopic site and metastasis to distant organs were evaluated by GFP fluorescence and histologically. A clone derived from human small cell lung cancer cell line showed significant metastatic activity and formed metastatic foci mainly in the bone, with a few incidences in adrenal gland, brain, lymph, and kidney. The metastatic characteristics of the clone are similar to the clinical aspects of small cell lung cancer.
Furthermore, through in vivo selection of this metastatic clone, we have succeeded to establish a series of variant clones with different metastatic potential. These clones have nearly identical tumorigenicity at the orthotopic site, adhesion activities to extracellular matrix, and anchorage-independent growth activities. Interestingly, these clones showed different invasion activities in a Matrigel chamber using conditioned medium as chemoattractant. Comprehensive analysis such as DNA microarray and cytokine antibody array revealed that there are some genes/factors differentially expressed among these variant.