Abstract: LiverMetastasis of Tumor Cells Promoted by Interaction between Colon Cancer Cells andHuman Liver Sinusoidal EndotheliumLichao SUN1, Shuting LI2, Long YU1, Lixin SUN1, Lulu HAN1, Tong LIU1, Zhihua YANG1, Yuliang RAN1Correspondence to: Lichao SUN, E-mail: sunlichao_1980@hotmail.com1State Key Laboratory of Molecular Oncology,2Department of Internal Medicine, Cancer Institute (Hospital), Chinese Academy of Med-ical Sciences, Peking Union Medical College, Beijing 100021, ChinaThis work was supported by National Program on Key Basic Research Project (973 Program) (No. 2009CB521804)Abstrtact Objective: To investigate the effect of co-culture between colon cancer cells and human liver sinusoidal endothelialcells on metastasis of the cancer cells, and to provide a basic experimental material for studying the mechanism of liver metastasis in co-lon cancer. Methods: The human sinusoidal endothelial cells and colon cancer cells were co-cultured in vitro for 21 rounds. Methods in-cluding Transwell migration assay, Gelatin zymography assay, CCK-8 proliferation assay and colony formation assay were used for test-ing the ability of invasion, proliferation, and the colony formation of cancer cells. The subcutaneous tumor formation assay and experi-mental liver metastasis assay were conducted to detect the ability of tumor growth and liver metastasis. The related molecular mecha-nism was examined by Western blot. Results: There was a clear boundary among the colon cancer cells SW1116P21, which had beencultured with the liver sinusoidal endothelial cells for 21 rounds. Compared with the SW1116 cells, the SW1116P21 parent cells werecharacterized by a greater invasive ability, cell proliferation and colony formation in soft agar, with a double enhancement in the abilityof the cell invasion. Gelatin zymography assay showed that the ability of the SW1116P21 cells to secrete MMP-2/9 was significantlyhigher than that of the parental cells. The assay of subcutaneous tumor formation showed that the ability of subcutaneous tumor forma-tion of SW1116P21 was significantly increased. It was found in the experimental liver metastases that the SW1116P21 cells had moreliver metastasis compared with the SW1116 cells. Western blot showed increased vimentin expression and decreased E-cadherin expres-sion in the SW1116P21 cells, compared with the SW1116 cells. Conclusion: The interaction between colon cancer cells and endothelialcells can promote tumor cell invasion, proliferation and colony formation in vitro, and tumor formation and liver metastasis in vivo. Theepithelial–mesenchymal transition ( EMT ) in SW1116P21 cells contributes to the change of characteristics of tumor cells.Keywords Colon cancer; Human liver sinusoidal endothelial cells; Co-culture; Liver metastasis