Analysis of biological characteristic features in cancer stem cell in digestive organs

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590809
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: HIGUCHI Hajime Keio University, 医学部, 助教 (20306682)
• Project Period (FY): 2008 – 2010
• Keywords: 癌幹細胞 / epithelial-to-mesenchymal transition / apoptosis / mesenchymal stem cell

Research Abstract

Cancer related materials, i.e., cell lines, endoscopic biopthy specimen, or, surgically resected specimen, were analyzed for ; i) expression of cancer stem cell markers, ii) tumor formation, iii) colony forming activity, iv) drug-resistance, and v) potentials for local invasion and metastasis. Our results suggest that side population (SP) cells isolated from pancreatic cancer have some cancer stem cell-like properties ; i) high tumorigenic/colony forming activity, ii) resistance to some chemotherapeutic drugs as well as apoptosis-inducing molecules such as TRAIL, iii) high metstatic potential, and iv) enhanced capability to undergo epithelial-to-mesenchymal transition (EMT) and invasion. In hepatocellular carcinoma, CD133-positive side population cells were highly tumorigenic and chemotherapy-resistant. These cancer stem cell-like features were enhanced by co-culturing with bone marrow-derived mesenchymal stem cells (MSCs) and/or MSC-derived myofibroblast-like cells, suggesting MSCs provide microenvironment so-called cancer stem cell niche to maintain stem cell phenotype in cancer derived SP cells. These results suggest that SP cells would be a therapeutic tagrget, especially to prevent cancer sten cell invasion and metastasis. Mesenchymal cell-derived microenvironment would be another terapeutic target to regulate cancer stem cell maintenance.

Research Products

• [Journal Article] (2010)
  • Author(s): Satoshi Kurita, Hajime Higuchi, Yoshimasa Saito, Nobuhiro Nakamoto, Hiromasa Takaishi, Shinichiro Tada, Hidetsugu Saito, Gregory J. Gores, Toshifumi Hibi
  • Journal Title: Cancer Sci 101 Pages: 1431-1439
  • Peer Reviewed
• [Journal Article] Side population of pancreatic cancer cells predominates in TGF-beta-mediated epithelial to mesenchymal transition and invasion. (2009)
  • Author(s): Ayano Kabashima, Hajime Higuchi, Hiromasa Takaishi, Yumi Matsuzaki, Sadafumi Suzuki, Motoko Izumiya, Hideko Iizuka, Gen Sakai, Shigenari Hozawa, Toshifumi Azuma, Toshifumi Hibi
  • Journal Title: Int-J-Cancer 124 Pages: 2771-2779
  • Peer Reviewed
• [Presentation] Wnt signaling contributes to the maintenance of cancer stem cell-like populations in Huh7 hepatocellular carcinoma cell line : Role of hepatic stellate cells. (2010)
  • Author(s): Masayuki Adachi, Hajime Higuchi, Ayano Kabashima, Shinsuke Funakoshi, Shoko Nakamura, Hiromasa Takaishi, Toshifumi Hibi
  • Organizer: AACR meeting abstract 2010, 203
  • Place of Presentation: Washington
  • Year and Date: 20100417-20100421
• [Presentation] Cancer stem cell like properties of 5-fluorouracil resistant Panc (2010)
  • Author(s): Motoko Izumiya, Hajime Higuchi, Ayano Kabashima, Toru Igarashi, Shoko Nakamura, Shinsuke Funakoshi, Masayuki Adachi, Hiromasa Takaishi, Toshifumi Hibi
  • Organizer: AACR meeting abstract 2010, 335 101^<st> American Association for Cancer Research
  • Place of Presentation: Washington
  • Year and Date: 20100417-20100421
• [Presentation] Mesenchymal stem cells induce epithelial-to-mesenchymal transition (EMT) in metastatic SP cells in pancreatic cancer. (2010)
  • Author(s): Ayano Kabashima, Hajime Higuchi, Yumi Matsuzaki, Shinsuke Funakoshi, Masayuki Adachi, Motoko Izumiya, Gen Sakai, Toru Igarashi, Shoko Nakamura, Hiromasa Takaishi, Toshifumi Hibi
  • Organizer: AACR meeting abstract 2010, 387 101st American Association for Cancer Research
  • Place of Presentation: Washington
  • Year and Date: 20100417-20100421
• [Presentation] Isolation and identification of Notch signal positive cells in pancreatic cancer cell line. (2009)
  • Author(s): Gen Sakai, Hajime Higuchi, Hiromasa Takaishi, Motoko Izumiya, Masaya Adachi, Ayano Kabashima, Shouko Nakamura, Toshifumi Hibi
  • Organizer: AACR meeting abstract 2009, 193 100^<th> American Association for Cancer Research.
  • Place of Presentation: Denver
  • Year and Date: 20090418-20090422
• [Remarks] ホームページ等