CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

Abstract

The chemokine CXCL12 and its receptors CXCR4 and CXCR7 might play important roles in the occurrence and development of oral squamous cell carcinoma (OSCC). While CXCR4 expression is associated to initiation and progression of OSCC, the role of CXCR7, the recently founded second CXCL12 receptor, has not yet been elucidated in OSCC. In this study, CXCR4 and CXCR7 expressions were evaluated using western blot and quantitative RT-PCR in OSCC cells. AMD3100 (CXCR4 antagonist) was used to inhibit the activation of CXCR4. In contrast to CXCR4, effective CXCR7 small interfering RNA (siRNA) segments were used to silence CXCR7 in OSCC cells. The biological effects of CXCL12-CXCR4/CXCR7 axis on OSCC cell lines were studied by CCK-8 and transwell assay. As determined by RT-PCR and Western blot, CXCR7 expression was significantly downregulated after siRNA transfection in OSCC cells, and thus significantly promoted OSCC cell migration and invasion in vitro. The relative roles of the two CXCL12 receptors were further assessed by CXCR7 knockdown or deactivate CXCR4 receptor alone, or in combination, in the OSCC cells. In vitro functional analyses indicated that, in response to their common ligand (CXCL12), both receptors induced inhibition of proliferation and migration in OSCC cells in a dose-dependent manner. Exogenous CXCL12 could promote cell migration and invasion. In conclusion, our results indicated that CXCL12 which combined its receptor CXCR4 and CXCR7 together could promote cell motilities of OSCC.

CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

“…CXCR4 was proved to be involved in cell proliferation and chemotherapy resistance in various cancers . In oral cancer, it is widely proved that CXCR4 contributes to cell motilities and promotes cell migration and invasion via epithelial‐mesenchymal transition . CXCR4 is a marker of tumor aggressiveness and indicates poor prognosis of tongue cancer patients .…”

“…18 In oral cancer, it is widely proved that CXCR4 contributes to cell motilities and promotes cell migration and invasion via epithelial-mesenchymal transition. 19,20 CXCR4 is a marker of tumor aggressiveness and indicates poor prognosis of tongue cancer patients. 4 Moreover, downexpression of CXCR4 inhibits the proliferation of oral cancer through increased microRNA-9 level.…”

CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma

“…CXCR4 has been linked to different tumour entities as a negative prognostic marker and important factor in carcinoma cell homing and subsequent metastasis ( Chen et al , 2015 ; Krieg et al , 2015 ; Mego et al , 2016 ). Thus far, little is known about the CXCR4/CXCR7/CXCL12 axis in MTC.…”

“…In addition to CXCR4, SDF1 α also binds to CXCR7, a chemokine receptor found to be significantly upregulated in different types of epithelial tumours ( Gebauer et al , 2011 ; Schrevel et al , 2012 ; Chen et al , 2015 ). It has been demonstrated that CXCR7 promotes tumour cell survival by inhibiting apoptosis and facilitates colony formation through increased focal adhesion properties ( Burns et al , 2006 ).…”

CXCR4/CXCR7/CXCL12-Axis in Follicular Thyroid Carcinoma

“…These observations have led to the idea that CXCR7 functions as a co-receptor to CXCR4, which increases CXCL12-mediate G-protein signalling 16 . Despite these controversies, increasing evidence of CXCR7 participation in tumour development, neovascularization and invasion has been accumulating 17 - 19 . Its overexpression in different types of malignant tumours has been well documented and its activation causes tumour cell proliferation, invasion and neo-angiogenesis 13 .…”