NEW IN VITRO 3D FUNCTIONAL MODEL OF TUMORIGENESIS

肿瘤发生的新体外 3D 功能模型

• 批准号: 6967439
• 负责人: RAJ K. SINGH
• 金额: $ 7.36万
• 依托单位: VIVO BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967439
• 关键词: MCF7 cell; angiogenesis; basement membrane; cell adhesion; cell differentiation; cell proliferation; disease /disorder model; extracellular matrix; fibroblasts; host neoplasm interaction; human tissue; mixed tissue /cell culture; model design /development; neoplasm /cancer invasiveness; neoplastic process; placenta; vascular endothelium

DESCRIPTION (provided by applicant): There is a need for developing an in vitro tumorigenesis model which mimics the in vivo biology of tumors. At present, tumor studies mostly utilize monolayer cell cultures and animal-derived biomatrix systems. The commonly used Matrigel and collagen models exhibit major compositional and biological limitations. Moreover, no well defined functional model is available for examining the important stages of tumor development in humans. DSI recently created a novel human biomatrix system, HuBiogel, for exploring cell-matrix interactions. Its physiologic matrix milieu, unlike existing models, actively supports proliferation, organization and differentiation of epithelial and endothelial cells. Employing this versatile biomatrix technology, DSI proposes to develop new physiologically-relevant (3D) models of human tumor invasion and angiogenesis. These tumor-host bioassay systems would allow analysis of discrete cellular and molecular events of tumor growth and progression in vitro. The Phase I specific goals are: 1. Develop and optimize HuBiogel assay systems using defined biomatrix formulations and 3D cell culture configurations and; 2. Demonstrate practical applications for monitoring key tumorigenesis events using multicellular tumor spheroid cocultures with fibroblasts or endothelial cells. In the second phase of this R&D project, functional studies of new bioassays will be expanded for validation with other human tumor models. The timely development of this clinically relevant model will positively impact cancer biology, drug discovery and therapeutic arenas. Commercial Importance & Significance: No acceptable commercial tumor model currently exists which utilizes a defined human biomatrix system. DSI will develop reusable and disposable 3D tumor invasion and angiogenesis bioassays. Sale of HuBiogel and pre-packed assay systems would have a significant world-wide market, both as a research and diagnostic tool.

描述（由申请人提供）： 需要开发模拟肿瘤的体内生物学的体外肿瘤发生模型。目前，肿瘤研究主要利用单层细胞培养和动物源性生物基质系统。常用的基质胶和胶原模型表现出主要的组成和生物学限制。此外，没有明确定义的功能模型可用于检查人类肿瘤发展的重要阶段。DSI最近创建了一种新的人类生物基质系统HuBiogel，用于探索细胞-基质相互作用。与现有模型不同，其生理基质环境积极支持上皮细胞和内皮细胞的增殖、组织化和分化。利用这种多功能的生物基质技术，DSI提出开发新的人体肿瘤侵袭和血管生成的生理相关（3D）模型。这些肿瘤宿主生物测定系统将允许在体外分析肿瘤生长和进展的离散细胞和分子事件。第一阶段的具体目标是：1。使用定义的生物基质配方和3D细胞培养配置开发和优化HuBiogel测定系统; 2.演示使用多细胞肿瘤球体与成纤维细胞或内皮细胞共培养物监测关键肿瘤发生事件的实际应用。 在该研发项目的第二阶段，将扩大新生物测定的功能研究，以验证其他人类肿瘤模型。这种临床相关模型的及时开发将对癌症生物学、药物发现和治疗领域产生积极影响。商业重要性和意义：目前不存在可接受的商业肿瘤模型，其使用定义的人类生物基质系统。DSI将开发可重复使用和一次性的3D肿瘤侵袭和血管生成生物测定。HuBiogel和预包装检测系统的销售将具有重要的全球市场，无论是作为研究工具还是诊断工具。