Profiling analysis of differential gene expression between hematogenous and peritoneal metastatic sublines of human pancreatic cancer using a DNA chip.

We established the novel sublines HPC-1H5, HPC-3H4, HPC-4H4, and Panc-1H5, which have a high potential of liver metastasis, and HPC-1P5a, HPC-3P4a, HPC-4P4a, and Panc-1P5a, which have a high potential of peritoneal dissemination, derived from low metastatic HPC-1, HPC-3, HPC-4, and Panc-1cell lines, respectively. To clarify the molecular mechanisms of cancer metastasis and of the different levels of gene expression in a variety of metastatic potentials in pancreatic cancer, we performed a broad analysis of differential gene expression analysis between parental cell lines and metastatic sublines. In comparison with the parental cell lines, 65 and 36 genes were overexpressed and underexpressed in highly liver-metastatic sublines. On the other hand, 43 and 45 genes were overexpressed and underexpressed in highly peritoneal-metastatic sublines. uPAR and Serin protease were overexpressed, and E2A and IGF1R were underexpressed in both metastatic sublines. Hierarchical clustering analysis revealed 22 genes classifying liver, peritoneal metastatic sublines and low-metastatic parental cell lines. These genes might be targeted genes separating those two major metastatic forms after surgery. A greater number of cell line samples and more genes will have to be utilized in future studies in order to understand the involvement of genes in cancer metastasis more thoroughly. However, these results will help to clarify the molecular mechanisms of pancreatic cancer metastasis.