Abstract
Metastasis accounts for most cancer related deaths. The common metastasis models utilize intravenous injection of tumor cells, bypassing the egression of malignant cells. We developed a unique metastasis model by in vivo passaging the Lewis lung carcinoma (3LL) cells and maintaining them in vivo with 7–11 days of intermittent culture. When injected subcutaneously, parental 3LL cells have minimal metastasis, while in vivo passaged 3LL cells (p‐ 3LL) show robust metastasis. To determine the differences between metastatic p‐3LL versus non‐metastatic 3LL, we compared the gene expression profiles by microarray analysis of RNA from these cells as well as the primary tumors from each. The array analysis revealed alteration in the expression of numerous genes previously known to be associated with tumor metastasis. The data also revealed several novel markers associated with increased metastasis including enhanced expression of two matrix metalloproteinases (MMPs), MMP‐9 and MMP‐12, and the decreased expression of MMP‐2. Given the role of MMPs in the remodeling of the extracellular matrix and cell motility, we further investigated the altered RNA and protein expression of MMPs in p‐3LLs and their tumors by real time PCR and Western blot analysis. Together, these suggest that these three MMPs may play an important role in lung cancer metastasis.
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