Open AccessBone mesenchymal stem cells are recruited via CXCL8‐CXCR2 and promote EMT through TGF‐β signal pathways in oral squamous carcinoma
Author(s) -
Meng Lin,
Zhao Yueqi,
Bu Wenhuan,
Li Xing,
Liu Xinchen,
Zhou Dabo,
Chen Yumeng,
Zheng Shize,
Lin Quan,
Liu Qilin,
Sun Hongchen
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12859
Subject(s) - mesenchymal stem cell , epithelial–mesenchymal transition , cancer research , flow cytometry , chemokine , cxc chemokine receptors , nude mouse , chemokine receptor , interleukin 8 , pathology , biology , in vivo , metastasis , immunology , medicine , cytokine , cancer , inflammation , microbiology and biotechnology , genetics
Abstract Objectives Bone mesenchymal stem cells (BMSCs) play critical roles in tumour microenvironment. However, molecular mechanisms of how BMSCs to be recruited and effect subsequent tumour progression are poorly understood in oral squamous cell carcinoma (OSCC). Materials and Methods The distribution of CXCL8 was detected by immunohistochemical staining in OSCC tissues. The chemotaxis of conditioned media from different epithelial cells to BMSCs was examined by trans‐well assay. Real‐time quantitative PCR (qPCR) and ELISA were used to detect the expression of related cytokines and chemokine receptors. The migration of BMSCs was observed in BALB/c nude mice. The roles of BMSCs in proliferation, migration and invasion of OSCC were detected by CCK‐8, flow cytometry and trans‐well assay. Epithelial‐mesenchymal transition (EMT)–related markers were analysed by qPCR and Western blot in vitro, and growth was evaluated in BALB/c nude mice using subcutaneously implanted OSCC in nude mouse model in vivo. Results Using OSCC, we show CXCL8, secreted by OSCC, binds to exclusively CXCR2 in BMSCs to facilitate migration of BMSCs to OSCC. TGF‐β secreted by BMSCs subsequently induces EMT of OSCC to promote their proliferation, migration and infiltration. We also showed that the Ras/Raf/Erk axis plays a critical role in tumour progression. Conclusions Our results provide the molecular basis for BMSC recruitment into tumours, and how this process leads to tumour progression and leads us to develop a novel OSCC treatment target.