Suppression of tumor cell proliferation and migration by human umbilical cord mesenchymal stem cells: A possible role for apoptosis and Wnt signaling

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) represent potential therapeutic tools for solid tumors. However, there are numerous inconsistent results regarding the effects of hUCMSCs on tumors, and the mechanisms underlying this remain poorly understood. The present study further examined this controversial issue by analyzing the molecular mechanisms of the inhibitory effects of hUCMSCs on the proliferation and migration of the human lung cancer A549 cell line and the human hepatocellular carcinoma (HCC) BEL7402 cell line in vitro. Flow cytometric analysis demonstrated that hUCMSCs arrested tumor cells in specific phases of the cell cycle and induced the apoptosis of tumor cells by using the hUCMSC-conditioned medium (hUCMSC-CM). The hUCMSC-CM also attenuated the migratory abilities of the two tumor cell types. Furthermore, the expression of B-cell lymphoma 2 (Bcl-2), the pro-form of caspase-7 (pro-caspase-7), β-catenin and c-Myc was downregulated, while that of ephrin receptor (EphA5), a biomarker of cancer cell dormancy, was slightly increased in these two tumor cell lines treated with hUCMSC-CM. Specifically, when co-cultured via direct cell-to-cell contact, hUCMSCs were able to spontaneously fuse with any of the two types of solid tumor cells. These observations suggested that hUCMSCs may be a promising candidate for the biological therapy of lung cancer and HCC. Future studies should focus on detailed evidence for cell fusion, as well as other mechanisms proposed in the present study, by introducing additional experimental approaches and models.