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The chemokine receptors CXCR 1 and CXCR 2 regulate oral cancer cell behaviour
Author(s) -
Khurram Syed A.,
Bingle Lynne,
McCabe Brenka M.,
Farthing Paula M.,
Whawell Simon A.
Publication year - 2014
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.12191
Subject(s) - chemokine , chemokine receptor , receptor , cancer research , biology , flow cytometry , matrigel , mapk/erk pathway , signal transduction , chemistry , immunology , microbiology and biotechnology , angiogenesis , biochemistry
Background Chemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin‐8 ( IL ‐8) receptors CXCR 1 and CXCR 2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR 1 and CXCR 2 expression on normal oral keratinocytes ( NOK s) and oral cancer cell lines ( OCCL ) and their relative response when exposed to IL ‐8 and growth‐related oncogene‐α (which selectively binds CXCR 2). Methods mRNA and protein expression was studied using RT‐PCR , immunocytochemistry and flow cytometry. ELISA s were used to investigate ERK 1/2 phosphorylation and MMP production, whereas a MTS ‐based assay was employed to study proliferation. Migration assays were carried out using modified B oyden chambers with a matrigel coating used for invasion assays. Results mRNA expression of CXCR 1 and CXCR 2 was seen in both NOK s and OCCL with significantly higher protein expression in OCCL . Exposure to IL ‐8 and GRO α increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOK s. These effects were mediated through CXCR 1 and CXCR 2 (for IL ‐8) and CXCR 2 (for GRO α) as receptor‐blocking antibodies significantly inhibited the responses. IL ‐8 and GRO α also increased MMP ‐9 release from NOK s and OCCL with significantly higher amounts released by OCCL . However, an increase in MMP ‐7 production was only seen in OCCL . Conclusions Functional CXCR 1 and CXCR 2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.