Dual effects of human adipose tissue-derived mesenchymal stem cells on NF-kB pathway in tumor growth of a549 lung adenocarcinoma cells and ht-29 colon cancer cells

Human adipose tissue-derived mesenchymal stem cells(hATMSCs) have a great potential as therapies for various diseases and regenerative medicine. However, emerging evidence suggests that human stem cells have both promoting and inhibitory effects on tumor growth. For the clinical use of hATMSCs as a novel cell therapy, it is important to determine in which tumor environment hATMSCs have tumor supporting effects or suppressing effects and to understand the underlying mechanism. We investigated the effect of hATMSCs on growth of 6 different types of tumor cell lines using in vivo xenograft models of A-375, A-431, A549, NCI-N87, HT-29 and Capan-1. The hATMSCs have an inhibitory effect on tumor growth of A549, but at the same time, a promoting effect on growth of HT-29. We focused on A549 and HT-29 tumor and performed further protein analysis. The activation level of tumor-related proteins such as NF-κB p65, JAK3, STAT3 and β-Catenin was analyzed by western blotting. The results showed there is an obvious correlation between the tumor growth and the activation of NF-κB, which is the expression level of phosphorylated NF-κB p65 was reduced in A549 tumor, but the level was increased in HT-29 tumor. Moreover, those dual effects were also supported by results from additional in vitro study using coculture and flow cytometric analysis. Altogether, we demonstrated the dual effects of hATMSCs, which is inhibiting effect on A549 and promoting effect on HT-29, and the correlation between the tumor growth and the expression level of NF-κB. Despite the controversies concerning the effect on tumor progression, the application of stem cells has broad prospective in many areas. Therefore, we consider that it is required further research to understand the interactions between stem cells and various types of tumors and those understandings will provide a new clue for stem cell therapy.