Contribution of Colon Cancer Cells to Mesenchymal Cells in the Formation of Hepatic Metastasis

Proliferations of cancer cells and mesenchymal cells are necessary for the formation of hepatic metastasis. Endothelial cells and hepatic stellate cells (HSCs), which exist in the extrasinusoidal space and produce extracellular matrix, are present in hepatic lobules as mesenchymal cells. In this study we investigated the contribution of colon cancer cells to endothelial cells and HSCs in the formation of hepatic metastasis. We collected serum-free conditioned medium (SFCM) of LM-H cells, which are highly liver metastatic colon cancer cells. The SFCM of LM-H cells significantly enhanced proliferation and migration of human umbilical vein endothelial cells (HUVECs) and enhanced the proliferation and migration of HSCs derived from rats. On investigating the growth factors in the SFCM of LM-H cells, we found vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The proliferation of HUVECs was inhibited by anti-VEGF antibody, and that of HSCs was inhibited by anti-PDGF antibody. The angiogenesis inhibitor TNP-470 significantly decreased the number of hepatic metastases of LM-H cells in nude mice. In conclusion, the VEGF and PDGF that colon cancer cells produce are important factors in the structural reorganization of hepatic metastasis. The angiogenesis inhibitor TNP-470 seems to be a potent agent for inhibiting hepatic metastasis of colon cancer.