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: 3945278
• 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/3945278
• 关键词: butyrates; cell adhesion; cell cell interaction; cell population study; cellular oncology; combination cancer therapy; 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 (Black PH, NEJM. 303:1315, 1980). Human glioma cells in tissue culture produce and shed in the media much greater amounts of glycosaminoglycans (GAGs) than normal glial cells (Glimelius et al Biochem J. 172:443, 1978). 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.

癌细胞表面脱落的各种产物 可能在粘附丧失、转移、 免疫阻断因子和其他病理生理学的产生 (Black PH, NEJM. 303:1315, 1980)。 人类 组织培养中的神经胶质瘤细胞在培养基中产生和脱落大量 比正常神经胶质细胞含有更多的糖胺聚糖 (GAG) 细胞（Glimelius 等人 Biochem J. 172:443, 1978）。 糖胺聚糖是聚阴离子化合物，通常结合 与蛋白质核心共价结合。 它们是一个重要的组成部分 细胞表面并参与细胞与细胞的相互作用。 那里 也是透明质酸酶敏感物质存在的证据 一些肿瘤细胞系（包括神经胶质瘤）上的保护层， 有人建议，保护性 GAG 外套可以 阻碍免疫反应和化疗的功效。 我们的目标是修改或防止合成和脱落 培养的人神经胶质瘤细胞中的 GAG，并可能呈现 他们更容易接受化疗等 具有免疫反应性。 为此，我们单独或组合使用 组合，分化剂二甲亚砜 (DMSO)、丁酸钠、视黄酸和地塞米松。 已知这些药物会影响其他细胞中 GAG 的合成。 系统。