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CCL2 promotes cell migration by inducing epithelial‐mesenchymal transition in oral squamous cell carcinoma
Author(s) -
Ling Zihang,
Yang Xi,
Chen Xiaobin,
Xia Juan,
Cheng Bin,
Tao Xiaoan
Publication year - 2019
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12869
Subject(s) - vimentin , ccl2 , paracrine signalling , epithelial–mesenchymal transition , cell migration , autocrine signalling , immunohistochemistry , cancer research , cell , chemokine , antibody , pathology , cell culture , biology , oral mucosa , cancer , metastasis , medicine , immunology , inflammation , receptor , biochemistry , genetics
Background Although a few studies suggested that the chemokine CCL2 might be involved in the development of oral squamous cell carcinoma (OSCC), the exact mechanism remains unclear. In this study, we aimed to determine the resource of CCL2 in lesions and explored a potential mechanism that CCL2 promotes tumor progression. The study was an effort to provide new insights into the pathological role of CCL2 in OSCC. Methods Specimens of OSCC and normal oral mucosa were stained using immunohistochemistry (IHC) to assess the CCL2 expression. Enzyme‐linked immunosorbent assay (ELISA) was used to detect the difference of CCL2 between OSCC and normal oral mucosa cell lines. In addition, we treated OSCC cells with exogenous rCCL2 combined with or without CCL2 neutralizing antibody and then determined the changes of in epithelial‐mesenchymal transition (EMT) markers and cell migration capacity using immunofluorescence, Western blotting, transwell migration, and wound healing assays. Results We have found that CCL2 expression was upregulated significantly in both lesions and cell culture supernatant of OSCC compared with controls. IHC staining demonstrated that CCL2 expression was primarily located in the cytoplasm and cell membrane of cells. We have also found that rCCL2 could effectively induce EMT through upregulating Snail in OSCC cells, which was demonstrated by the decrease of E‐cadherin and the increase of vimentin. In addition, we have found that CCL2 neutralizing antibody could block EMT induced by CCL2 in OSCC. Conclusions CCL2 secreted by cancer cells can promote cell migration by inducing EMT via paracrine or autocrine in OSCC.