Development of artificial 3-dimensional cancer tissue model as tool for pathological analysis and therapeutic research for malignant solid tumor

• Project/Area Number: 14571143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: NOSHIRO Hirokazu Faculty of Medicine University Hospital, Ass., 大学病院, 助手 (90301340)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Takehisa KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (60142189) ; SUEISHI Katsuo KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (70108710) ; KATANO Mitsuo KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (10145203) ; 内山 明彦 九州大学, 医学部附属病院, 助手 (20294936) ; 森崎 隆 九州大学, 大学院・医学研究院, 助手 (90291517)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
• Keywords: microgravity / 3-dimension / TGF-β / IFN-γ / invasion / pancreas cancer / gastric cancer / artificial tissue / 転移 / 人工がん組織 / スキルス / SMAD / 人工癌組織 / 三次元培養 / 低重力培養 / TGF-b / IFN-g

Research Abstract

Carcinoma tissue consists essentially of carcinoma cells, stromal cells, and the extracellular matrix. Stromal cells such as fibroblast, vasucular endothelial cells, macrophages are an integral part of carcinoma tissue and account for some of its most destructive features. An in vitro organotypic culture model which mimic carcinoma tissue is needed to understand the complexities of cancer. In these studies, we developed two types of in vitro models of carcinoma tissue : (1) a new in vitro model of pancreatic carcinoma tissue using a rotary cell culture system with four disposable vessels (RCCS^<TM>-4D) that provide a simulated microgravity condition. (2) a three-dimensional gastric carcinoma model similar to invasive gastric carcinoma tissue Results and Discussion : (1) Using RCCS-4D system, we indicated that the simulated microgravity condition mimics the in vitro microenvironment more closely than the conventional static 1g condition. (2) We reconstituted an in vitro preclinical invasive gastric carcinoma model in which we were able to observe morphological changes of both carcinoma cells and fibroblasts in real time for more than 30 days. Using this model, we were able to show that exogenous IFN-g suppresses TGF-β-dependent carcinoma cell invasion through a possible integration of TGF-β and IFN-γ signals, which could be considered as crross-talk in the Smad pathway. In conclusion, our three-dimensional carcinoma model should prove valuable in further study of cell-cell and cell-matrix interactions in complicated carcinoma tissue and provide a development of possible therapeutic strategy.

Research Products

• [Publications] Nakamura K, Kuga H, Morisaki T, Katano M et al.: "Simulatd microgravity culture system for 3-D carcinoma tissue model"Biotechniques. 33(5). 1068-1070 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kuga H, Morisaki T, Katano M et al.: "Interferon-γ suppresses transforming-β-induced invasion of gastric carcinoma cells through cross-talk of Smad pathway In a three-dimensional culture model"Oncogene. 22. 7838-7847 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamanaka N, Morisaki T, Katano M et al.: "Interleukin-1b enhances invasive ability of gastric carcinoma through nuclear factor kB activation"Clinical Cancer Research. 10(5). 1853-1859 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakamura K, Kuga H, Morisaki T, et al.: "Simulated microgravity culture system For 3D carcinoma tissue model"Biotechniques. 33(5). 1068-1070 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kuga H, Morisaki T, Noshiro H, et al.: "Interferon-gamma suppress transforming-b-induced invasion Of gastric carcinoma cells through cross-talk of Smad pathway in a three-dimensional culture model"Oncogene. 22. 7838-7847 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamanaka N, Morisaki T, Noshiro H, et al.: "Interleukin-1b enhances inavasive ability of gastric carcinoma through nucleaqr factor kB activation"Clinical Cancer Research. 10(5). 1853-1859 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakamura K, Kuga H, Morisaki T, Katano M et al.: "Simulatd microgravity culture system for 3-D carcinoma tissue model"Biotechniques. 33(5). 1068-1070 (2002)
• [Publications] Kuga H, Morisaki T, Katano M et al.: "Interferon-γ suppresses transforming-β-induced invasion of gastric carcinoma cells through cross-talk of Smad pathway in a three-dimensional culture model"Oncogene. 22. 7838-7847 (2003)
• [Publications] Yamanaka N, Morisaki T, Katano M et al.: "Interleukin-1b enhances invasive ability of gastric carcinoma through nuclear factor kB activation"Clinical Cancer Research. (in press). (2004)
• [Publications] Nakamura K, Morisaki T et al.: "Simulated microgravity culture system for a 3-D carcinoma tissue model"Bio Techniques. 33.no5. 1068-1076 (2002)