Molecular mechanism of solitary cell infiltration in pancreatic cancer

• Project/Area Number: 24790362
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Keio University
• Principal Investigator: MASUGI Yohei 慶應義塾大学, 医学部, 助教 (90528598)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 人体病理学 / 弧在性浸潤 / 上皮間葉移行 / 膵癌 / 予後 / マイクロアレイ / SMAD3 / ITGB4 / 膵がん

Outline of Final Research Achievements

This study focuses on "Solitary cell infiltration", which is a characteristic pathological finding of pancreatic cancer cells singly infiltrating into the tissue stroma. High degree of solitary cell infiltration is known to reflect the tumor aggressiveness of pancreatic cancer. However the molecular mechanism is unclear.
Among vast number of molecules expressed in cance cells, we found the two important molecules, SMAD3 and Integrin beta 4 (ITGB4), as key player in the mechanism of solitary cell infiltration. We showed that these molecules are related to the promotion of a characteristic invasive property (EMT), and that both SMAD3 and ITGB4 are novel prognostic markers in pancreatic cancer. Our results are expected to contribute to the molecular diagnosis of tumor aggressiveness and the exploitation of novel molecular targets in clinical cancer of the pancreas.

Research Products

• [Journal Article] Upregulation of integrin beta4 promotes epithelial-mesenchymal transition and is a novel prognostic marker in pancreatic ductal adenocarcinoma (2015)
  • Author(s): Masugi Y, Yamazaki K, Emoto K, Effendi K, Tsujikawa H, Kitago M, Itano O, Kitagawa Y, Sakamoto M
  • Journal Title: Labolatory Investigation Volume: 95 Issue: 3 Pages: 308-19
  • DOI: 10.1038/labinvest.2014.166
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Upregulated SMAD3 promotes epithelial-mesenchymal transition and predicts poor prognosis in pancreatic ductal adenocarcinoma (2014)
  • Author(s): Yamazaki K, Masugi Y, Effendi K, Tsujikawa H, Hiraoka N, Kitago M, Shinoda M, Itano O, Tanabe M, Kitagawa Y, Sakamoto M
  • Journal Title: Laboratory investigation Volume: 印刷中 Issue: 4 Pages: 817-25
  • DOI: 10.1016/j.humpath.2013.11.017
  • Peer Reviewed / Open Access
• [Presentation] Up-regulation of integrin beta 4 promotes epithelial-mesenchymal transition and is a novel prognostic marker in pancreatic cancer. (2014)
  • Author(s): 真杉洋平，山崎剣，江本桂，エッフェンディカトリーヌ，辻川華子，坂元亨宇.
  • Organizer: 第60回日本病理学会秋期特別総会
  • Place of Presentation: 国立劇場おきなわ(沖縄)
  • Year and Date: 2014-11-20 – 2014-11-21
• [Presentation] Up-regulation of integrin beta 4 promotes epithelial-mesenchymal transition and is a novel prognostic marker in pancreatic cancer. (2014)
  • Author(s): Masugi Y, Yamazaki K, Emoto K, Effendi K, Kitago M, Itano O, Kitagawa Y, Sakamoto M.
  • Organizer: American Association of Cancer Research Annual meeting
  • Place of Presentation: San Diego Convention Center (San Diego, USA)
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Up-regulation of integrin beta 4 promotes epithelial-mesenchymal transition and is a novel prognostic marker in pancreatic cancer (2014)
  • Author(s): Yohei Masugi, Ken Yamazaki, Katsura Emoto, Kathryn Effendi, Hanako Tsujikawa, Minoru Kitago, Osamu Itano, Yuko Kitagawa, Michiie Sakamoto
  • Organizer: American Association for Cancer Research annual meeting 2014
  • Place of Presentation: サンディエゴ（アメリカ）
• [Presentation] SMAD3 upregulation is a novel biomarker of poor prognosis and epithelial-mesenchymal transition in pancreatic cancer (2013)
  • Author(s): Ken Yamazaki, Yohei Masugi, Kathryn Effendi, Michiie Sakamoto
  • Organizer: American Association for Cancer Research annual meeting 2013
  • Place of Presentation: ワシントンDC（アメリカ）
• [Presentation] SMAD3 upregulation is a novel biomarker of poor prognosis and epithelial-mesenchymal transition in pancreatic cancer (2013)
  • Author(s): Ken Yamazaki, Yohei Masugi, Kathryn Effendi, Michiie Sakamoto.
  • Organizer: American Association of Cancer Research annual meeting 2013
  • Place of Presentation: Washington DC, USA
• [Remarks] 慶應義塾大学医学部病理学教室 慶應義塾大学病院病理診断部
  • URL: http://www.keio-pathology.net/index.html