title: The chemokine receptors CXCR1 and CXCR2 regulate oral cancer cell behaviour.
abstract: BACKGROUND
  Chemokines regulate physiological and pathological leucocyte trafficking, and chemokine receptors play a role in tumorigenesis. Expression of interleukin-8 (IL-8) receptors CXCR1 and CXCR2 has been shown in oral squamous cell carcinoma (OSCC) but remains poorly characterised. This aim of this study was to investigate CXCR1 and CXCR2 expression on normal oral keratinocytes (NOKs) and oral cancer cell lines (OCCL) and their relative response when exposed to IL-8 and growth-related oncogene-α (which selectively binds CXCR2).
  
  
  METHODS
  mRNA and protein expression was studied using RT-PCR, immunocytochemistry and flow cytometry. ELISAs were used to investigate ERK1/2 phosphorylation and MMP production, whereas a MTS-based assay was employed to study proliferation. Migration assays were carried out using modified Boyden chambers with a matrigel coating used for invasion assays.
  
  
  RESULTS
  mRNA expression of CXCR1 and CXCR2 was seen in both NOKs and OCCL with significantly higher protein expression in OCCL. Exposure to IL-8 and GROα increased intracellular ERK phosphorylation, proliferation, migration and invasion with OCCL showing a greater response than NOKs. These effects were mediated through CXCR1 and CXCR2 (for IL-8) and CXCR2 (for GROα) as receptor-blocking antibodies significantly inhibited the responses. IL-8 and GROα also increased MMP-9 release from NOKs and OCCL with significantly higher amounts released by OCCL. However, an increase in MMP-7 production was only seen in OCCL.
  
  
  CONCLUSIONS
  Functional CXCR1 and CXCR2 exist on normal and cancerous oral epithelial cells, and our data suggests a role for these receptors in oral cancer biology.
authors: Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
authors: Syed A
authors: SA
authors: Khurram
authors: Lynne
authors: L
authors: Bingle
authors: Brenka M
authors: BM
authors: McCabe
authors: Paula M
authors: PM
authors: Farthing
authors: Simon A
authors: SA
authors: Whawell
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054360:Chemokine CXCL1 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005881:Gingiva / Q000166:cytology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D020783:Matrix Metalloproteinase 7 / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D023062:Receptors, Interleukin-8A / Q000187:drug effects / Q000502:physiology*; D023063:Receptors, Interleukin-8B / Q000187:drug effects / Q000502:physiology*
chemical_list: C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: CXCR1; CXCR2; Chemokine; IL-8; chemokine receptor; oral squamous cell carcinoma