CCL2 promotes cell migration by inducing epithelial‐mesenchymal transition in oral squamous cell carcinoma

Abstract

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.

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

“…Interestingly, various chemokines have been implicated to contribute to EMT progression in cancer cells. EMT can be induced by CXCL8 and its receptors through overexpression of the transcription factor Brachyury [141], CCL2 with the enhancement of Snail expression [142], the CXCL6/CXCR1/2 axis via the PI3K/AKT and Wnt/β-catenin pathways [143], and the CXCL1/LCN2 paracrine axis with the activation of Src signalling [144]. In addition, NF-κB is associated with the EMT induced by CCL5 and CCL18 [145,146].…”

Notch3 Knockout Suppresses Mouse Mammary Gland Development and Inhibits the Proliferation of 4T1 Murine Mammary Carcinoma Cells via CCL2/CCR4 Axis

“…CCL2, a 13-kDa CC family of chemokines and also known as monocyte chemotactic protein-1 (MCP-1/CCL2), is produced mainly by monocytes/macrophages but is also expressed by endothelial, fibroblasts, epithelial, smooth muscle, mesangial, astrocytic, and microglial cells. Recently, Ling et al (2019) showed that oral squamous carcinoma cells can express and release CCL2 to effectively induce epithelial-mesenchymal transition. Moreover, there is a growing body of evidence that CCL2 has the ability to recruit monocytes and macrophages during development, inflammation, and tumorigenesis (Ferreira et al, 2008).…”

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

“…Future studies will be required to evaluate the inflammatory response across racially divergent breast cancer cell lines or tissues. What we do know, however, is that compounds like apigenin that attenuate the CCL2/CCR2 axis would slow the aggressive nature of TNBC and hormone positive breast cancers (27,28) by attenuating invasion, metastasis, EMT and the development of drug resistance (59)(60)(61)(62). CCL2 inhibitors have been tested in various tumors, tumor cells and xenograft models with CCL2 lowering effects brought about by losartan (63) anlotinib (64) imatinib (65) zoledronic acid (66) oroxylin A (67) aspirin (68) natural compounds in coffee (kahweol acetate, cafestol) (69) or conophylline from Ervatamia microphylla (70) which can reduce invasive inflammatory tumor infiltration.…”