Metastasis-promoting role of extravasated platelet activation in tumor

Tomoharu Miyashita, Hidehiro Tajima, Isamu Makino, Hisatoshi Nakagawara, Hirohisa Kitagawa, Sachio Fushida, John W. Harmon, Tetsuo Ohta

Research output: Contribution to journalArticle

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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)289-294
Number of pages6
JournalJournal of Surgical Research
Volume193
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Epithelial-to-mesenchymal transition
  • Metastasis
  • Pancreatic cancer
  • Platelet aggregation

ASJC Scopus subject areas

  • Surgery

Cite this

Miyashita, T., Tajima, H., Makino, I., Nakagawara, H., Kitagawa, H., Fushida, S., Harmon, J. W., & Ohta, T. (2015). Metastasis-promoting role of extravasated platelet activation in tumor. Journal of Surgical Research, 193(1), 289-294. https://doi.org/10.1016/j.jss.2014.07.037