STUDIES ON HUMAN GLIOMA AND RAT PROSTATE ADENOCARCINOMA CELLS IN VITRO

人胶质瘤和大鼠前列腺腺癌细胞的体外研究

• 批准号: 3922566
• 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/3922566
• 关键词: adenocarcinoma; biological response modifiers; butyrates; cell adhesion; cell cell interaction; cell population study; cellular oncology; combination cancer therapy; dexamethasone; dimethylsulfoxide; glioma; human tissue; hyaluronate; membrane activity; mucopolysaccharides; neoplasm /cancer chemotherapy; neoplasm /cancer immunology; neoplastic cell; prostate neoplasms; 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 an 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. Similar studies were also conducted on cell line PA III derived from a transplantable adenocarcinoma of the rat prostrate gland. The cell line can reproduce the original tumor type when innoculated into Loboud Wistar rats and makes it feasible, if necessary, to extend our studies in vivo.

从癌细胞的细胞表面脱落各种产物 可能在粘附丧失、转移， 产生免疫阻断因子和其他病理生理学 癌症的方面（Black PH，NEJM. 303：1315。1980年）。 人脑胶质瘤 组织培养中的细胞在培养基中产生和脱落的量要大得多， 糖胺聚糖（GAGs）的数量比正常的神经胶质细胞 （Glimelius等人Biochem J. 172：443，1978）。 糖胺聚糖是 聚阴离子化合物，通常与蛋白质核心共价结合。 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 还有证据表明 透明质酸酶敏感的保护层的存在， 包括神经胶质瘤在内的肿瘤细胞系， 保护性GAG涂层可能会阻碍免疫反应， 化疗的疗效。 我们的目标是改变或阻止 人胶质瘤细胞中糖胺聚糖的合成和脱落 文化，并可能使他们更容易受到 化疗和免疫反应更强。 为此目的 我们单独或组合使用差异化试剂， 二甲基亚砜（DMSO）、丁酸钠、视黄酸和 地塞米松。 已知这些试剂影响以下物质的合成： 其他系统中的GAGs。 类似的研究也进行了细胞 来源于大鼠可移植腺癌的PA III系 前列腺 该细胞系可以复制原始肿瘤 型时，接种到Loboud Wistar大鼠，使其 可行的，如果必要的话，扩大我们的研究在体内。