Mast cells induce epithelial-to-mesenchymal transition and migration in non-small cell lung cancer through IL-8/Wnt/ß-catenin pathway.

ABSTRACT

Background: In the various cancer, mast cells (MCs) infiltration is correlated with a worse prognosis. There is an increasing evidence that MCs and their mediators are participated in remodeling of the tumor microenvironment and facilitate tumor growth, epithelial-to-mesenchymal transition (EMT) and metastasis. Methods: The transwell was conducted to evaluate the correlations between MCs and non-small cell lung cancer (NSCLC) cells in vitro. The RNA interference of ß-catenin was performed to further explore the signaling pathway. Lung adenocarcinoma cell line A549 and human MC (HMC-1) were subcutaneously injected into BALB/c nude mice. The conventional experiment methods (such as quantitative RT-PCR Western Blot, Immunofluorescence, and ELISA) were used in the present study. Results: We found that high density of MCs in NSCLC correlates with worse prognosis. The NSCLC cells could release CCL5 and recruit MCs to the tumor microenvironment. Then, we explored that HMC-1 transplantation accelerated the growth of A549 cell in nude mice. Moreover, the MCs-derived factors were responsible for tumor growth. When NSCLC cells were activated, MCs produced various factors that induced EMT and migration. We also identified that CXCL8/interleukin (IL)-8 served as the major modulator containing in the activated MC conditioned medium. Furthermore, MCs and exogenous IL-8 promoted ß-catenin phosphorylation in NSCLC cells. Inhibiting the Wnt/ß-catenin pathway by RNA interference could revert EMT and migration of NSCLC. Conclusions: Our study suggests that MCs are recruited into NSCLC microenvironment and improve the EMT and migration of cancer cells, thereby accelerating the growth of NSCLC.