BIOLOGICAL MODIFICATION OF HUMAN GLIOMA CELLS IN VITRO

人胶质瘤细胞的体外生物学修饰

• 批准号: 3969029
• 负责人: G CONSTANTOPOULOS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3969029
• 关键词: butyrates; cell adhesion; cell cell interaction; cell population study; cellular oncology; dexamethasone; dimethylsulfoxide; glioma; growth media; human tissue; hyaluronate; membrane activity; mucopolysaccharides; neoplasm /cancer chemotherapy; neoplasm /cancer immunology; neoplastic cell; retinoate; tissue /cell culture

Shedding of various products from the cell surface of cancer cells may have an important role in loss of adhesion, metastasis, generation of immune-blocking factors and other pathophysiologic aspects of cancer. Human glioma cells in tissue culture produce and shed in the media much greater amounts of glycosaminoglycans (GAGs) than normal glial cells. Glycosaminoglycans are polyanionic compounds, usually bound covalently to a protein core. They are a prominent component of the cell surface and are implicated in cell-cell interaction. There is also evidence for existence of hyaluronidase-sensitive protective coats on some neoplastic cell lines including gliomas, and it has been suggested that the protective GAG coat may impede the immune response and the efficacy of chemotherapy. Our objective was to modify or prevent the synthesis and shedding of GAGs in human glioma cells in culture, and possibly to render them more susceptible to chemotherapy and more immunologically responsive. For this purpose we use singly or in combination, the differentiating agents dimethyl sulfoxide (DMSO), sodium butyrate, retinoic acid, and dexamethasone. These agents are known to affect the synthesis of GAGs in other systems.

从癌细胞的细胞表面脱落的各种产物可能具有 在粘附丧失、转移、生成 免疫阻断因子和癌症的其他病理生理学方面。 组织培养中的人脑胶质瘤细胞在培养基中大量产生和脱落， 比正常神经胶质细胞更大量的糖胺聚糖（GAG）。 糖胺聚糖是聚阴离子化合物，通常共价结合到 蛋白质核心 它们是细胞表面的重要组成部分， 与细胞间的相互作用有关 也有证据表明 透明质酸酶敏感的保护涂层上的一些肿瘤细胞系 包括神经胶质瘤，并且已经表明保护性GAG涂层 可能会阻碍免疫反应和化疗的疗效。 我们 目的是改变或防止GAGs的合成和脱落， 人类神经胶质瘤细胞培养，并可能使他们更容易受到 化疗和免疫反应更好。 为此我们 单独或组合使用分化剂二甲基亚砜 （DMSO）、丁酸钠、视黄酸和地塞米松。 这些试剂 已知影响其它系统中GAG的合成。