Effects of bone marrow-derived mesenchymal stem cells on invasion and metastasis of gastric cancer cells and its mechanism

Objective To investigate the role of bone marrow mesenchymal stem cells (BM-MSCs) in the invasion and metastasis of gastric cancer cells and to explore its mechanism. Methods SGC7901 and KATO-Ⅲ gastric cancer cells were co-cultured with BM-MSCs respectively, and the invasion ability of SGC7901 and KATO-Ⅲ gastric cancer cells were detected by Transwell assay. Secondly, CD133+ and CD133- cells were sorted from KATO-Ⅲ gastric cancers and co-cultured with BM-MSCs respectively to compare their changes in invasiveness. Meanwhile, the expressions of p-AKT and epithelial-mesenchymal transition(EMT) relative factors in gastric cancer cells were detected by Western-blot. The role of CD133 in BM-MSCs affecting the ability of invasion of gastric cancer cells was further vertified by the overexpression of CD133 in SGC7901 cells. SPSS17.0 software was used for statistical processing, and the stand deviation of the measurement data were expressed as the standard deviation, independent sample t test was conducted. Results The invasiveness of co-cultured SGC7901 and KATO-Ⅲ cells was significantly enhanced. The invasive ability of KATO-Ⅲ CD133+ cells co-cultured with BM-MSCs tended to increase more significantly than that of co-cultured CD133- cells[(259.0±24.0)vs(58.0±5.6), P<0.001]. The expressions of p-AKT, Snail and N-cadherin were significantly increased in co-cultured CD133+ cells (P=0.003, P=0.003, P=0.002), while the expression of E-cadherin was reduced (P=0.021). After co-cultured with BM-MSCs, the expression of E-cadherin was also reduced in CD133- cells (P=0.005), but the expressions of p-AKT, Snail and N-cadherin were no significantly changes (P=0.744, P=0.277, P=0.295). SGC7901 co-cultured with BM-MSC after overexpression of CD133 showed higher invasiveness than blank control group[(239.3±24.0) vs (103.3±15.5), P<0.001]. The expressions of p-AKT, Snail and N-cadherin were significantly increased when co-cultured with BM-MSCs in the group of CD133 overexpression (P=0.001, P=0.001, P=0.001), while the expression of E-cadherin was significantly decreased(P=0.003). The expressions of Snail and N-cadherin were also significantly increased after co-cultured with BM-MSCs in the blank control group (P=0.001, P=0.004), and the expression of E-cadherin was significantly decreased (P=0.018), while the expression of p-AKT was not significantly changed (P=0.193). Conclusions BM-MSCs can enhance the invasion and metastasis of gastric cancer cells by promoting the EMT of gastric cancer cells. CD133 may be involved in the regulation of EMT in gastric cancer cells through the PI3K/AKT signaling pathway. Key words: Stomach neoplasms; Mesenchymal stem cells; Bone marrow; Epithelial-mesenchymal transition; CD133