Establishment of high metastatic evolved clone of adenocarcinoma cells with Mmp9 promoter-driven fluorescence reporter

抄録

Metastasis is the crucial phenomena in cancer malignancy. The principal function of matrix metalloproteinases (Mmps) is to promote tumor growth, invasion, and metastasis. In the present study, we have established a novel cell-based reporter system indicated by Mmp9 expression and activities within high-metastatic clone of murine colon adenocarcinoma cells. A high-metastatic clone LuM1 expressed Mmp9 gene and gelatinase activity at significantly high levels as compared to those in a low-metastatic clone NM11 and a parental clone. Using the high-metastatic LuM1, we established a cell-based reporter system indicated by promoter activities of Mmp9, designated LuM1/m9. The clone LuM1/m9 is also highly metastatic to lungs in both circulating tumor cell model and subcutaneous transplant model, forming nodules that are positive with green fluorescent reporter driven by the Mmp9 promoter. The LuM1/m9 clone is partly sensitive to dexamethasone, an NF-kB inhibitor, calcium ionophore ionomycin and imatinib, but partly resistant to these drugs. A novel high-metastatic clone of murine colon adenocarcinoma cells, in which an Mmp9 promoter-driven fluorescence reporter indicates invasive and metastatic cells, is useful for in vitro/ in vivo imaging and functional screening.