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

开发人工3维癌组织模型作为恶性实体瘤病理分析和治疗研究的工具

• 批准号: 14571143
• 负责人: NOSHIRO Hirokazu
• 金额: $ 2.3万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571143/
• 关键词: 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

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.

癌组织主要由癌细胞、间质细胞和细胞外基质组成。间质细胞，如成纤维细胞、血管内皮细胞、巨噬细胞是癌组织不可分割的一部分，是其最具破坏性的特征之一。为了更好地理解癌症的复杂性，需要一种模拟癌组织的体外器官型培养模型。在这些研究中，我们建立了两种类型的癌组织体外模型：(1)一种新的胰腺癌组织体外模型，使用带有四个一次性血管的旋转细胞培养系统（RCCS^<TM>-4D），提供模拟微重力条件。结果与讨论：(1)使用RCCS-4D系统，我们发现模拟的微重力条件比常规的静态1g条件更接近于体外微环境。(2)构建体外临床前侵袭性胃癌模型，实时观察癌细胞和成纤维细胞形态变化30天以上。通过该模型，我们能够证明外源性IFN-g通过TGF-β和IFN-γ信号的可能整合抑制TGF-β依赖的癌细胞侵袭，这可能被认为是Smad途径中的串扰。总之，我们的三维肿瘤模型将在进一步研究复杂肿瘤组织中细胞-细胞和细胞-基质相互作用方面证明有价值，并为可能的治疗策略提供发展。

项目成果

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)

Kuga H、Morisaki T、Noshiro H 等人：“干扰素-γ 在三维培养模型中通过 Smad 通路的串扰抑制转化-b 诱导的胃癌细胞的侵袭”癌基因。

Nakamura K, Morisaki T et al.: "Simulated microgravity culture system for a 3-D carcinoma tissue model"Bio Techniques. 33.no5. 1068-1076 (2002)

Nakamura K、Morisaki T 等人：“3D 癌组织模型的模拟微重力培养系统”生物技术。

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)

Yamanaka N、Morisaki T、Noshiro H 等人：“Interleukin-1b 通过核因子 kB 激活增强胃癌的侵袭能力”临床癌症研究。

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)

Yamanaka N、Morisaki T、Katano M 等人：“Interleukin-1b 通过核因子 kB 激活增强胃癌的侵袭能力”临床癌症研究。

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)

Yamanaka N、Morisaki T、Katano M 等人：“Interleukin-1b 通过核因子 kB 激活增强胃癌的侵袭能力”临床癌症研究。