Modeling meningioma growth orthotopically in the nude mouse

裸鼠脑膜瘤原位生长建模

• 批准号: 7179246
• 负责人: ANITA LAL
• 金额: $ 7.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7179246
• 关键词: Anaplastic Meningioma; Behavior; Benign Meningiomas; Biological Models; Biology; Brain; Brain Neoplasms; Cell Line; Cells; Central Nervous System Neoplasms; Cerebrospinal Fluid; Characteristics; Clinical; Development; End Point; Environment; Gene Mutation; Genetic; Goals; Green Fluorescent Proteins; Growth; Human; Hypoxia; In Vitro; Intention; Intracranial Meningiomas; Intraventricular; Investigation; Knock-out; Knowledge; Label; Laboratory Research; Life; Location; Malignant Neoplasms; Meninges; Modeling; Molecular; Morbidity - disease rate; Mus; Mutation; NF2 gene; Neurologic; Nude Mice; Operative Surgical Procedures; Outcome; Pattern; Pre-Clinical Model; Protocols documentation; Rate; Recurrence; Reporting; Research; Resources; Riots; Risk; Rodent; Scanning; Solid Neoplasm; Subdural space; Surface; System; Techniques; Testing; Therapeutic; Toxicity Tests; Translating; Treatment Protocols; World Health Organization; Xenograft Model; Xenograft procedure; established cell line; gene function; host neoplasm interaction; improved; in vivo; local drug delivery; meningioma; mortality; mouse model; neoplastic cell; novel; novel therapeutics; relating to nervous system; skull base; tool; tumor; tumor growth; tumorigenesis

DESCRIPTION (provided by applicant): Meningiomas are the second most common brain tumor and are a considerable cause of morbidity and mortality, yet experimental investigations into their biology have been hampered by the lack of appropriate model systems. Meningioma tumor cells do not grow well in culture, usually senescing after a few passages. Although there are a few established meningioma cell lines, there is no well-characterized description of their growth as orthotopic xenografts. Meningioma tumor growth is particular to the subdural space that contains the cerebrospinal fluid. Modeling tumor growth in this microenvironment is associated with widespread dissemination, an uncommon growth pattern for human meningiomas. Although challenging to model orthotopically, it is essential to create a relevant model in order to advance our knowledge about these tumors. The available genetic meningioma mouse model, a knockout of the NF2 gene in arachnoidal cells, has limited utility because only 20% of these mice develop meningiomas after over a year. This R03 application proposes to develop and characterize a fluorescent orthotopic meningioma xenograft model in athymic mice. It is our intention to define a reliable and reproducible technique for producing intracranial meningiomas, to define the pattern of meningioma growth at three different orthotopic locations and to characterize the biology of the xenografts. We hypothetize that the unique environment of the subdural space is essential for meningioma growth. In addition, our protocol will locally constrain meningioma growth and allow us to visualize solid tumor masses, which have not previously been attained. Labeling tumor cells with green fluorescent protein will allow us to definitively observe tumor behavior and growth in vivo using fluorescent body scanning. The fluorescent label will also facilitate our assessment of dissemination upon histological examination. We anticipate this model system will be applicable to dissect the functional genetics of meningioma tumorigenesis and to serve as a preclinical model for testing the toxicity and efficacy of conventional and novel therapeutic protocols. This system will also serve as a tool to investigate techniques of local drug delivery specifically to meningiomas which grow on the surface of the brain or the skull base, and for investigations into the unique tumor-host interactions of meningiomas. The development of this model system is a resource badly needed to move the field of meningioma research forward.

描述（由申请人提供）：脑膜瘤是第二常见的脑肿瘤，是发病率和死亡率的重要原因，但由于缺乏适当的模型系统，对其生物学的实验研究受到阻碍。脑膜瘤肿瘤细胞在培养中生长不好，通常在几代传代后衰老。虽然有一些确定的脑膜瘤细胞系，但没有很好地描述它们作为原位异种移植物的生长。脑膜瘤肿瘤生长在含有脑脊液的硬膜下间隙。在这种微环境中模拟肿瘤生长与广泛传播有关，这是人类脑膜瘤的一种不常见的生长模式。尽管正位建模具有挑战性，但为了提高我们对这些肿瘤的认识，创建一个相关的模型是至关重要的。现有的遗传性脑膜瘤小鼠模型，在蛛网膜细胞中敲除NF2基因，效用有限，因为这些小鼠中只有20%在一年多后发展为脑膜瘤。本R03应用程序建议在胸腺小鼠中开发和表征荧光原位脑膜瘤异种移植模型。我们的目的是确定一种可靠的、可重复的颅内脑膜瘤生成技术，确定脑膜瘤在三个不同原位位置的生长模式，并描述异种移植物的生物学特性。我们假设硬膜下空间的独特环境对脑膜瘤的生长至关重要。此外，我们的方案将局部限制脑膜瘤的生长，并使我们能够看到以前没有达到的实体瘤肿块。用绿色荧光蛋白标记肿瘤细胞将使我们能够使用荧光体扫描明确地观察肿瘤的行为和生长。荧光标记也将有助于我们在组织学检查时评估传播情况。我们预计该模型系统将适用于解剖脑膜瘤肿瘤发生的功能遗传学，并作为测试传统和新型治疗方案的毒性和有效性的临床前模型。该系统还将作为研究局部药物递送技术的工具，专门针对生长在脑表面或颅底的脑膜瘤，以及研究脑膜瘤独特的肿瘤-宿主相互作用。该模型系统的开发是推动脑膜瘤研究领域向前发展所急需的资源。