J Cancer 2019; 10(16):3830-3841. doi:10.7150/jca.29953

Research Paper

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

Jingjing Qu1,2#, Tianli Cheng3#, Li Liu2, Jianfu Heng1,2, Xiaobao Liu1, Ziyi Sun2, Wenxiang Wang4✉, Kunyan Li1✉, Nong Yang2✉

1. Department of Clinical Pharmaceutical Research Institution, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410008, China
2. Department of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410008, China
3. Thoracic Medicine Department 1, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410008, China
4. The Second Department of Thoracic Surgery, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410008, China
# Jingjing Qu and Tianli Cheng contributed equally to this work.

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 β-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 β-catenin phosphorylation in NSCLC cells. Inhibiting the Wnt/β-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.

Keywords: mast cells, non-small cell lung cancer, epithelial-to-mesenchymal transition, IL-8/Wnt/β-catenin pathway, cell migration

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How to cite this article:
Qu J, Cheng T, Liu L, Heng J, Liu X, Sun Z, Wang W, Li K, Yang N. Mast cells induce epithelial-to-mesenchymal transition and migration in non-small cell lung cancer through IL-8/Wnt/β-catenin pathway. J Cancer 2019; 10(16):3830-3841. doi:10.7150/jca.29953. Available from http://www.jcancer.org/v10p3830.htm