title: Stimulation by Monocyte Chemoattractant Protein-1 Modulates the Ex-vivo Colony Formation by Head and Neck Squamous Cell Carcinoma Cells.
abstract: BACKGROUND
  The outcome of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. To improve therapy of HNSCC, biomarkers indicating progression of the disease or modifiers with potential as therapeutic targets and therapy need to be investigated. Since monocyte chemoattractant protein (MCP1) is potentially involved in tumorigenesis of HNSCC, we aimed to clarify its role in HNSCC and investigated the influence of stimulation by MCP1 and its depletion using antibodies against MCP1 (anti-MCP1) on colony formation by HNSCC cells.
  
  
  METHODS
  Biopsies of HNSCC were treated according to the protocol of the FLAVINO assay with cisplatin, docetaxel, temsirolimus or cilengitide alone, or combined with MCP1 or anti-MCP1. After a 72-h incubation, ethanol-fixed and fluoresceine-isothiocyanate (FITC)-labeled epithelial colonies were counted.
  
  
  RESULTS
  Colony formation was significantly suppressed by MCP1 and 3.3 μM cisplatin, while docetaxel, cilengitide and temsirolimus at concentrations of 0.275, 10 and 0.50 μM caused insignificant effects. Addition of MCP1 to cisplatin, docetaxel and cilengitide increased efficacy of cytostatics in inhibition of colony formation, whereas those with temsirolimus were increased by anti-MCP1 that when applied alone failed to modulate colony formation. Overall regarding facilitated chemosensitivity, there was a statistical trend in favor of MCP1 stimulation over depletion.
  
  
  CONCLUSIONS
  Our ex vivo results show context-dependent effects of MCP1 in HNSCC cells. An increase of MCP1 level or its addition to cisplatin, docetaxel and cilengitide reduce colony formation but the efficacy of temsirolimus is augmented by MCP1 depletion. These context-dependently opposite outcomes call for further translational investigations in HNSCC.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany gunnar.wichmann@medizin.uni-leipzig.de.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wichmann
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Körner
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Boehm
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mozet
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dietz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2
keywords: FLAVINO assay; HNSCC; MCP1; anti-MCP1; ex-vivo chemoresponse