Identification of bone marrow-derived involved in pancreatic cancer progression and establishment of a new therapy

• Project/Area Number: 16K19937
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: Iwamoto Chika 九州大学, 医学研究院, 特任助教 (10752842)
• Research Collaborator: OHUCHIDA Kenoki ; OKUMURA Takashi ; ENDO Sho ; KOIKAWA Kazuhiro ; TAKESUE Shin
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膵癌 / 浸潤 / 膵臓癌 / 転移 / 癌

Outline of Final Research Achievements

In breast cancer, a subset of stromal cells was descended from bone marrow (BM)-derived cells. While BM-derived cells seem to be involved in remodeling of microenvironment and tumor progression in pancreatic cancer, this mechanism remains unknown. We aimed to investigate an association between pancreatic cancer progression and BM-derived cells.
The engraftment of BM-derived GFP+ cells was detected in recipients’ peripheral blood, BM, pancreas, liver, and ascites. In recipients’ pancreas, GFP+ cells were accumulated around ADM/PanIN and at invasive front. Invasive capability of cancer cells co-cultured with BM-derived cells significantly increased compared to the control. The present data also suggest that BM-derived cells is involved in infiltration of cancer cells.

Research Products

• [Journal Article] Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo180 (2018)
  • Author(s): Koikawa K, Ohuchida K, Takesue S, Ando Y, Kibe S, Nakayama H, Endo S, Abe T, Okumura T, Horioka K, Sada M, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Ohuchida R, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
  • Journal Title: Cancer Letters Volume: 412 Pages: 143-154
  • DOI: 10.1016/j.canlet.2017.10.010
  • Peer Reviewed / Open Access
• [Journal Article] Basement membrane destruction by pancreatic stellate cells leads to local invasion in pancreatic ductal adenocarcinoma (2018)
  • Author(s): Koikawa K、Ohuchida K、Ando Y、Kibe S、Nakayama H、Takesue S、Endo S、Abe T、Okumura T、Iwamoto C、Moriyama T、Nakata K、Miyasaka Y、Ohtsuka T、Nagai E、Mizumoto K、Hashizume M、Nakamura M
  • Journal Title: Cancer Letters Volume: 425 Pages: 65-77
  • DOI: 10.1016/j.canlet.2018.03.031
  • Peer Reviewed / Open Access
• [Journal Article] Postmortem interval estimation using the animal model of postmortem gas volume changes. (2017)
  • Author(s): Iwamoto C, Ohuchida K, Okumura M, Usumoto Y, Kishimoto J, Murata M, Ikeda N, Hashizume M.
  • Journal Title: Legal Medicine Volume: - Pages: 66-70
  • DOI: 10.1016/j.legalmed.2017.12.010
  • Peer Reviewed / Open Access
• [Journal Article] Autophagy is required for activation of pancreatic sstellate cells, associated with pancreatic cancer progression and promotes growth of pancreatic tumors in mice. (2017)
  • Author(s): Endo S, Nakata K, Ohuchida K, Takesue S, Nakayama H, Abe T, Koikawa K, Okumura T, Sada M, Horioka K, Zheng B, Mizuuchi Y, Iwamoto C, Murata M, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
  • Journal Title: Gastroenterology Volume: 印刷中 Issue: 6 Pages: 1492-1506
  • DOI: 10.1053/j.gastro.2017.01.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of FFPE Blocks of Resected Pancreas using Micro CT (2017)
  • Author(s): K. Shindo, K. Ohuchida, H.R. Roth, H. Oda, C. Iwamoto, M. Oda, M. Nakamura, K. Mori, M. Hashizume.
  • Journal Title: J JSCAS Volume: 19 Pages: 244-245
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Accumulation and integration of various medical images for pancreatic cancer. (2017)
  • Author(s): C. Iwamoto, K. Ohuchida, T. Okumura, N. Mochidome, S. Endo, H. Nakayama, S. Takesue, M. Murata, Y. Oda, M. Hashizume.
  • Journal Title: J JSCAS Volume: 19 Pages: 360-360
  • Peer Reviewed
• [Journal Article] Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells. (2017)
  • Author(s): Okumura T, Ohuchida K, Sada M, Abe T, Endo S, Koikawa K, Iwamoto C, Miura D, Mizuuchi Y, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
  • Journal Title: Oncotarget Volume: 8 Issue: 11 Pages: 18280-18295
  • DOI: 10.18632/oncotarget.15430
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Accumulation and integration of various medical images derived from KPC mice and resected human pancreases. (2018)
  • Author(s): Chika Iwamoto
  • Organizer: 4th International Symposium on the Project “Multidisciplinary Computational Anatomy”
  • Int'l Joint Research
• [Presentation] Pathological Digital Data Accumulation of Pancreatic Cancer and its Application to Multidisciplinary Computational Anatomy (2017)
  • Author(s): Chika Iwamoto
  • Organizer: The 3rd International Symposium on Multidisciplinary Computational Anatomy
  • Place of Presentation: 奈良
  • Year and Date: 2017-03-08
  • Int'l Joint Research
• [Presentation] BM-derived cells are involved in the tumor microenvironment and promote invasion of pancreatic cancer. (2017)
  • Author(s): Chika Iwamoto
  • Organizer: Annual Meeting of the American Pancreatic Association
  • Int'l Joint Research
• [Presentation] 膵癌組織における様々な病理像とMR像の集積とデジタル画像統合による予測モデルの検討 (2017)
  • Author(s): 岩本 千佳
  • Organizer: 日本コンピュータ外科学会
• [Presentation] 腫瘍多元計算解剖学モデルによる知能化手術 (2017)
  • Author(s): 岩本 千佳
  • Organizer: 日本コンピュータ外科学会