Stroma elimination therapy for cancer; a surrounding cancer cells by decoy engineered Mesenchymal Stem Cells, including suicide gene

• Project/Area Number: 25670567
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: University of Tsukuba
• Principal Investigator: Oda Tatsuya 筑波大学, 医学医療系, 教授 (20282353)
• Co-Investigator(Kenkyū-buntansha): KIDA Yasuyuki 国立研究開発法人産業技術総合研究所, 幹細胞工学センター, 研究チーム長 (20396526)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 癌線維芽細胞（CAF） / 間葉系幹細胞（MSC) / 癌-間質のクロストーク / 膵癌 / 癌線維芽細胞(CAF) / 間葉系幹細胞(MSC) / 癌-;間質のクロストーク

Outline of Final Research Achievements

Crosstalk between cancer cells and Cancer-Associated Fibroblast (CAF) plays a crucial role that comprises 3D organization of solid cancers. We designed new cancer therapy namely “decoy MSC therapy”, that involves administration of engineered MSC at first, and eliminate them after cancer cells are surrounded by decoy MSC. The origin of CAFs have been assumed as bone marrow derived Mesenchymal Stem Cell (BM-MSC), however they anc not be a souse of decoy MSC because of technical challenges. We employed adipose tissue derived MSC(AD-MSC), confirming its positive potential for the application in new therapy.

Research Products

• [Journal Article] Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer. (2016)
  • Author(s): Miyamoto R, Oda T, Hashimoto S, Kurokawa T, Inagaki Y, Shimomura O, et al.
  • Journal Title: Cancer Sci Volume: 107(4) Issue: 4 Pages: 514-520
  • DOI: 10.1111/cas.12888
  • NAID: 120007135356
  • Peer Reviewed / Open Access
• [Journal Article] Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1. (2014)
  • Author(s): Akashi Y, Oda T, Ohara Y, Miyamoto R, Kurokawa T, Hashimoto S, Enomoto T, Yamada K, Satake M, Ohkohchi N
  • Journal Title: Br J Cancer Volume: 110(6) Issue: 6 Pages: 1481-1487
  • DOI: 10.1038/bjc.2014.49
  • Peer Reviewed
• [Journal Article] Histological advantages of the tumor graft: a murine model involving transplantation of human pancreatic cancer tissue fragments. (2013)
  • Author(s): Akashi Y, Oda T, Ohara Y, Miyamoto R, Hashimoto S, Enomoto T, Yamada K, Kobayashi A, Fukunaga K, Ohkochi N.
  • Journal Title: Pancreas. Volume: 42(8) Issue: 8 Pages: 1275-1282
  • DOI: 10.1097/mpa.0b013e318296f866
  • Peer Reviewed
• [Journal Article] Histological and prognostic importance of CD44(+) /CD24(+) /EpCAM(+) expression in clinical pancreatic cancer (2013)
  • Author(s): Ohara Y, Oda T, Sugano M, Hashimoto S, Enomoto T, Yamada K, Akashi Y, Miyamoto R, Kobayashi A, Fukunaga K, Morishita Y, Ohkohchi N.
  • Journal Title: Cancer Sci. Volume: 104(8) Issue: 8 Pages: 1127-1134
  • DOI: 10.1111/cas.12198
  • Peer Reviewed
• [Patent(Industrial Property Rights)] がんの診断及び治療方法 (2016)
  • Inventor(s): 小田竜也，舘野浩章，平林淳，他5名
  • Industrial Property Rights Holder: 小田竜也，舘野浩章，平林淳，他5名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-069683
  • Filing Date: 2016-03-30