Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8

Background: bone marrow mesenchymal stem cells (bm-mscs) have been identified to be closely associated with tumor growth and progression. however,the roles of tumor-resident mscs in cancer have not been thoroughly clarified. this study was to investigate the regulating effect of gastric cancer-derived mscs (gc-mscs) on gastric cancer and elucidate the underlying mechanism. methods: gc-mscs were isolated from primary human gastric cancer tissues and characterized. the effect of gc-mscs on gastric cancer cell proliferation was analyzed by mtt assay and colony formation assay. transwell migration assay was performed to evaluate the influence of gc-mscs in gastric cancer cell migration. the regulating effects of interactions between gastric cancer cells and gc-mscs on their pro-angiogenic abilities were analyzed in a co-culture system,with the expression,and secretion of pro-angiogenic factors detected by rt-pcr and luminex assay. tube formation assay was used to further validate the angiogenic capability of gastric cancer cells or gc-mscs. cytokine profiles in the supernatant of gc-mscs were screened by luminex assay and neutralizing antibody was used to identify the key effective cytokines. the activations of akt and erk1/2 in gastric caner cells were detected by western blot. results: gc-msc treatment enhanced the proliferation and migration of bgc-823 and mkn-28 cells,which was more potently than mscs from adjacent non-cancerous tissues (gcn-mscs) or bone marrow (bm-mscs). higher expression levels of pro-angiogenic factors were detected in gc-mscs than gcn-mscs or bm-mscs. after 10 % gc-msc-cm treatment,bgc-823,and mkn-28 cells expressed increased levels of pro-angiogenic factors and facilitated tube formation more potently than cancer cells alone. furthermore,gc-mscs produced an extremely higher level of interleukin-8 (il-8) than gcn-mscs or bm-mscs. blockade of il-8 by neutralizing antibody significantly attenuated the tumor-promoting effect of gc-mscs. in addition,10 % cm of il-8-secreted gc-mscs induced the activations of akt or erk1/2 pathway in bgc-823 and mkn-28 cells. conclusion: tumor-resident gc-mscs promote gastric cancer growth and progression more efficiently than gcn-mscs or bm-mscs through a considerable secretion of il-8,which could be a possible target for gastric cancer therapy. © 2015 li et al.; licensee biomed central.