title: Metastasis-promoting role of extravasated platelet activation in tumor.
abstract: BACKGROUND
  The last decade has focused attention on the central role of platelets interacting with the tumor cells and the immune system in promoting tumor progression and distant spread through release of growth factors, such as transforming growth factor beta, vascular endothelial growth factor A, and plasminogen activator inhibitor 1, into the tumor microenvironment. We focused on the potential metastasis-promoting role of extravasated platelet aggregation in pancreatic cancer and stroma.
  
  
  METHODS
  Resected pancreatic cancer specimens from 40 patients were used in this study. To examine the expression and localization of platelet aggregation in the epithelial-mesenchymal transition (EMT) region in cancer and stroma, CD42b, Snail1, and E-cadherin were assessed using immunohistochemistry. We determined the correlation of these expressed proteins with clinical features.
  
  
  RESULTS
  CD42b expression was detected at the invasive front of the tumor, which was in 73% of the EMT portion, but not in the region of tubular formation. Increased Snail1 and reduction and/or loss of E-cadherin expressions were noted in 85% and 75% of the EMT portion, respectively. There was a significant correlation between CD42b and Snail1 expressions (P = 0.02) and CD42b and reduction and/or loss of E-cadherin expressions (P = 0.008).
  
  
  CONCLUSIONS
  We demonstrate that extravasated platelet aggregation is associated with the first step in the formation of the EMT. These data suggest a potential role for antiplatelet agents to suppress EMT and metastasis by changing the tumor microenvironment.
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan. Electronic address: tomoharumiya@gmail.com.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Makino
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Nakagawara
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
authors.affiliation: Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000276:immunology / Q000556:secondary*; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology*; D010974:Platelet Aggregation / Q000276:immunology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D015820:Cadherins; D019038:Platelet Glycoprotein GPIb-IX Complex; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: Epithelial-to-mesenchymal transition; Metastasis; Pancreatic cancer; Platelet aggregation