Microarray analyses reveal liver metastasis-related genes in metastatic colorectal cancer cell model

摘要

Purpose: To study the molecular mechanisms of colorectal cancer liver metastasis. Methods: Cecal wall implantation was performed in nude mice to subclone a highly liver metastatic human colorectal cancer clone (SW1116-M) from SW1116. In vivo and in vitro assays were adopted to confirm the proliferation and metastasis potential. The human tumor metastasis PCR microarrays were used to analyze the differential gene expressions. The results were confirmed further by real-time quantitative PCR. Results: SW1116-M and SW1116-S5, two human colon cancer cell clones with different metastatic potential, were subcloned from SW1116. In SW1116-M, in vitro invasion, migration and in vivo metastatic potential were higher, and in vitro proliferation rate was lower than SW1116-S5. In tumor metastasis PCR microarray, 24 genes related to cell invading, adhesion, cellular growth and differentiation were found with a twofold difference between SW1116-S5 and SW1116-M. Sixteen of these, including E-cadherins, MTSS1, TRAIL and TRPM1, were up-regulated; eight genes including cathepsin L, EphB2, HGF, MET, MCAM and RORβ were down-regulated. Conclusions: We have established a highly liver metastatic clone. The subsequent metastasis PCR microarray analysis identified a procedure of cellular differentiation and mesenchymal to epithelial transition (MET) in liver metastasis. The colonization to from macrometastasis is not a switch from cell cycle arrest but a result of cell differentiation and MET.