title: Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer.
abstract: BACKGROUND
  Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR(+)) chemokine family are powerful promoters of the angiogenic response.
  
  
  METHODS
  The expression of the CXC (ELR(+)) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines.
  
  
  RESULTS
  Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line.
  
  
  CONCLUSIONS
  CXC (ELR(+)) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment.
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College, Dublin, Ireland.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Baird
authors.forename: Steven G
authors.initials: SG
authors.lastname: Gray
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
mesh_terms: D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000032:analysis* / Q000235:genetics*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D016209:Interleukin-8; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics; D011499:Protein Processing, Post-Translational; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B
chemical_list: C475829:CXCL1 protein, human; C499706:CXCL2 protein, human; C499707:CXCL3 protein, human; C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B