title: Co-localization of macrophage inflammatory protein-3alpha (Mip-3alpha) and its receptor, CCR6, promotes pancreatic cancer cell invasion.
abstract: OBJECTIVE
  Macrophage inflammatory protein-3alpha (Mip-3alpha) is par t of a family of chemotactic cytokines involved in recruiting inflammatory cells throughout the body. CCR6 is a G-protein-linked, seven-transmembrane receptor that is highly specific for Mip-3alpha. The role of Mip-3alpha has been well defined in several inflammatory conditions, but its role has not been well defined in neoplastic processes. Mip-3alpha has been shown to promote pancreatic cancer cell migration, but no studies have demonstrated the effect of Mip-3alpha on pancreatic cancer cell invasion. We hypothesize that Mip-3alpha and its CCR6 receptor promote pancreatic cancer cell invasion.
  
  
  METHODS
  Immunohistochemical staining was per formed for Mip-3alpha and CCR6 in pancreatic cancer tissue and the human pancreatic cancer cell line PANC-1. RNA was isolated from PANC-1 cancer cells, and the presence of Mip-3alpha messenger RNA in PANC-1 cancer cells was determined by reverse transcriptase polymerase chain reaction. PANC-1 cancer cell invasion of type IV collagen was evaluated in the presence of Mip-3alpha and anti-CCR6 antibody with the use of a modified Boyden chamber invasion assay.
  
  
  RESULTS
  Co-localization of Mip-3alpha and its CCR6 receptor in pancreatic cancer was confirmed using immunohistochemical staining for Mip-3alpha and its CCR6 receptor and reverse transcriptase polymerase chain reaction for Mip-3alpha. Immunohistochemical staining of pancreatic cancer tissue and the PANC-1 cancer cell line showed positive staining for Mip-3alpha and its CCR6 receptor within the cancer cells. Staining was also positive for Mip-3alpha within stromal cells adjacent to the cancer cells in pancreatic cancer tissue. Reverse transcriptase polymerase chain reaction demonstrated the presence of Mip-3alpha messenger RNA within PANC-1 cancer cells. Invasion studies showed that increasing concentrations of Mip-3alpha promoted a dose-dependent increase in pancreatic cancer cell invasion of type IV collagen. The addition of 100 ng/mL of Mip-3alpha promoted a threefold increase in pancreatic cancer cell invasion over that of the control group. Anti-CCR6 antibody inhibited Mip-3alpha-stimulated PANC-1 cancer cell invasion of type IV collagen by 63%.
  
  
  CONCLUSIONS
  Co-localization of Mip-3alpha and its CCR6 receptor promotes pancreatic cancer cell invasion of type IV collagen. This finding continues to highlight the importance that inflammation plays in the progression of pancreatic cancer. As the relationship between the inflammatory and neoplastic processes involved with pancreatic cancer becomes better defined, therapies targeting the inflammatory process may help prevent pancreatic cancer invasion and metastasis.
authors.affiliation: Department of Surgery, Section of Surgical Oncology, Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: Troy F
authors.initials: TF
authors.lastname: Kimsey
authors.forename: A S
authors.initials: AS
authors.lastname: Campbell
authors.forename: D
authors.initials: D
authors.lastname: Albo
authors.forename: M
authors.initials: M
authors.lastname: Wilson
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D024141:Collagen Type IV; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology*; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D024141:Collagen Type IV; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine