The Effects Of UC-MSCs On Hepatoma Cell Lines And Role Of Chemokines In The Interaction

Mesenchymal stem cells(MSCs)are multipotent adult stem cells which could homing to injured tissues and tumors.Because of their low immunogenicity,ability to migrate to tumors and low frequency of tumorigenesis,more and more researches focus on MSCs as drug carriers to target tumors[1].The morbidity of liver cancer is high in China.The metastatic abilities between different types and stages of hepatocellular carcinoma(HCC)are different.Many studies indicated that MSCs could inhibit or promote growth of different kinds of cancers cells[2-6],thus we want to know whether MSCs could inhibit growth of hepatoma cell lines with different metastatic abilities.We co-cultured umbilical cord derived mesenchymal stem cells(UC-MSCs)with MHCC97H,SK-HEP-1,MHCC97L and QGY-7701 hepatoma cell lines and identified the effects of UC-MSCs on proliferation,apoptosis,cell cycle and colony formation of these hepatoma cell lines with different metastatic abilities.The results showed UC-MSCs could inhibit proliferation of these cell lines,arrest them in different cell cycles,induce their apoptosis and reduce their colony formation rates significantly.These results indicated that UC-MSCs could inhibit growth of HCC cells with different metastatic abilities and have potential of targeted therapy on liver cancer.On the other hand,we observed morphologies of these co-cultured HCC cells are changed,they seemed to have features of mesenchymal cells,this phenomenon suggested they may acquire higher metastatic abilities.Therefor we used wound-healing assay and transwell assay to investigate the effects of UC-MSCs on migration of different hepatocellular cell lines.The results showed UC-MSCs could promote migration of these HCC cells,indicated that despite UC-MSCs inhibiting growth of HCC cells,they promoted their metastasis.Afterward,we used human chemokine antibody array to examine the expression of chemokines in co-cultured systems contained UC-MSCs with MHCC97H and MHCC97L,which are hepatocellular cell lines with different metastatic abilities.We observed expressions of several chemokines were elevated in co-cultured systems.Finally,we selected MCP-3 to conduct further researches,which was increased significantly and have not been reported in metastasis of HCC so far.The data showed that adding MCP-3 could increase cell migrations both in MHCC97H and MHCC97L.As adding mouse anti-human MCP-3 into cocultured systems,the number of migrated cells was reduced.This study indicated that MCP-3 could promote metastasis of HCC cells,on condition that blocking MCP-3 or relevant receptors,the efficacy of UC-MSCs in liver cancer therapy may be elevated.