title: Monocyte chemotactic protein 1 (MCP-1) modulates pro-survival signaling to promote progression of head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Monocyte chemotactic protein-1 (MCP-1) recruits monocytes and macrophages to inflammation sites, and inflammatory infiltration correlates with the progression of head and neck squamous cell carcinoma (HNSCC). This study aims to determine whether MCP-1 expression is related to HNSCC malignancy and patient survival. We also investigated the relationship between MCP-1 expression and the phosphorylation state of the pro-survival pathway factors Akt, ERK, and STAT3.
  
  
  METHODS
  Expression of MCP-1 and related proteins in HNSCC cell lines was investigated using western blotting. HNSCC patients (34) without distant metastasis at diagnosis were recruited for tissue specimen evaluation of MCP-1 expression and clinical outcomes. The relationship between MCP-1 expression and survival was evaluated using the Cox proportional hazard model with stepwise selection.
  
  
  RESULTS
  High-grade HNSCC cell lines were found to have higher levels of active Akt, ERK, and/or STAT3 than did lower grade cell lines under serum-free condition. OCSL, the most malignant cell line, had the highest level of endogenous MCP-1. Administration of exogenous recombinant MCP-1 increased phosphorylation of Akt, ERK, and STAT3 in a dose- and time-dependent manner and increased cellular resistance to serum starvation. Inhibition of Akt, ERK, or STAT3 reduced cell growth and caused cell death. Long-term survival of HNSCC patients was negatively associated with the histological intensity of MCP-1, implicating MCP-1 as a potential prognostic marker for HNSCC.
  
  
  CONCLUSIONS
  These results suggest that overexpressed MCP-1 in cancer cells may promote HNSCC progression through upregulating pro-survival signaling pathways. High cellular MCP-1 expression is related to poor overall survival rate in HNSCC patients.
authors.affiliation: Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, College of Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan.
authors.forename: Wen-Tsai
authors.initials: WT
authors.lastname: Ji
authors.affiliation: Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, College of Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan.
authors.forename: Hau-Ren
authors.initials: HR
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.
authors.forename: Chun-Hsuan
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Life Sciences, Tzu-Chi University, Hualien, Taiwan ; Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Jeng-Woei
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan ; School of Medicine, Tzu Chi University, Hualian, Taiwan.
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt