Mesenchymal stem cells in inflammatory microenvironment potently promote metastatic growth of cholangiocarcinoma via activating Akt/NF-κB signaling by paracrine CCL5.

ABSTRACT: Our previous work has demonstrated that mesenchymal stem cells (MSCs) could induce metastatic growth of the inflammation-related cholangiocarcinoma (CCA). However, the functional mechanism of MSCs on CCA progression in the early inflammatory microenvironment remained undetermined. Here, we showed that TNF-α and IFN-γ-induced inflammatory microenvironment stimulated the expression of TNF-α, CCL5, IL-6, IDO, and activated the NF-κB signaling with p65 nuclear translocation in MSCs cells. CCA cell lines QBC939 and Mz-chA-1 exposed to the conditioned medium of MSCs after being stimulated by TNF-α and IFN-γ (TI-CM) exhibited enhanced mobility. Moreover, MSCs pre-stimulated by both inflammatory cytokines (TI-MSCs) increased tumor metastasis in vivo. The conditioned medium of TI-MSCs stimul

SUBMITTER: Zhong W 

PROVIDER: S-EPMC5650292 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature