A Role for the Chemokine Receptor CXCR2 in Oral Cancer

Oral squamous cell carcinoma is associated with high morbidity and mortality. Along with its limited prognosis, there is a lack of treatment options in advanced cases. These features make it essential to improve our understanding on the mechanisms involved in invasion and progression of this group of tumors. Although there is convincing experimental evidence on the relevance of CXC chemokines and their receptors in various cancers, there is still no reports on the relevance of CXCR2 in tumors of the oral cavity.

Objectives: to determine the role of the chemokine receptor CXCR2 in oral squamous cell carcinoma.

Methods: Human oral squamous carcinoma cells (HN30 lineage) were grown in 10% FBS DMEM and subsequently incubated with different concentrations of either the selective CXCR2 antagonist SB225002 (25, 50, 100, 200, 400, 800, 1600 and 32000nM and control DMSO 0001%) or the CXCR2 agonist CXCL-8/IL-8 (1, 3, 10, 30,100ng/mL and control PBS). The cell proliferation was accomplished by the MTT assay.

Results: The incubation of the selective CXCR2 antagonist SB225002 produced a concentration-dependent decrease of the HN30 cell lineage proliferation that was maximal at 800nM (about 40 % of inhibition). Relevantly, the chemokine CXCL-8/IL-8 caused a marked increase of HN30 proliferation, in a concentration-related manner, which reached the peak at 30nM (approximately 140 %).

Conclusions: Our findings indicate a clear role for the CXCR2 receptor in oral cancer progression. It is tempting to suggest that selective and orally active CXCR2 antagonists might represent an interesting alternative for the treatment of oral cancer, especially if combined with currently available therapy.

This work was supported by CAPES and CNPq, Brazil.