CELL INTERACTIONS WITH THROMBOSPONDIN

细胞与血小板反应蛋白的相互作用

• 批准号: 3808574
• 负责人: D D ROBERTS
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3808574
• 关键词: affinity chromatography; carbohydrate receptor; cell adhesion; cell cell interaction; cell migration; chemotaxis; glycolipids; glycoproteins; heparan sulfate; lung neoplasms; melanoma; messenger RNA; metastasis; neoplasm /cancer invasiveness; neoplastic cell; proteoglycan; receptor; receptor binding; sulfates; thrombospondins; tissue /cell culture

The functions of thrombospondin in cell adhesion and migration and tumor metastasis are being investigated. We have identified two regions of the thrombospondin molecule that mediate adhesive and migratory responses of cultured human melanoma cells to thrombospondin. The carboxyl-terminal domain mediates attachment and haptotaxis, while the amino-terminal domain mediates cell spreading and chemotaxis. The cell receptors recognizing these two regions of thrombospondin are under investigation. One class of receptors are sulfated glycoconjugates which bind to the amino-terminal domain of thrombospondin. A minor heparan sulfate proteoglycan that binds thrombospondin with high affinity was identified in two melanoma cell lines (Cancer Res. 48:6875, 1988). An unusual sulfated glycolipid present only in melanoma cell lines that spread on thrombospondin binds to thrombospondin and mediates melanoma cell spreading (ibid.). To further define the mechanism of thrombospondin interactions with tumor cells, receptors for the carboxyl-terminus of thrombospondin are being characterized. Small cell lung carcinoma cells which attach on thrombospondin but not on other adhesive proteins will be used to identify specific thrombospondin receptors. The intracellular responses of cells to binding of thrombospondin on the two types of receptors are also being investigated. Expression of thrombospondin mRNA in tumor cells is being examined to look for association of thrombospondin synthesis with in vivo metastatic potential.

血小板反应蛋白在细胞粘附、迁移和肿瘤中的作用 正在研究转移。 我们已经确定了两个区域的 血小板反应蛋白分子介导粘附和迁移反应， 培养的人黑色素瘤细胞对血小板反应蛋白的反应。 羧基末端 结构域介导附着和趋触性，而氨基末端 结构域介导细胞铺展和趋化性。 细胞受体 识别血小板反应蛋白的这两个区域正在研究中。 一类受体是硫酸化的糖缀合物，其结合到 血小板反应蛋白的氨基末端结构域。 少量硫酸乙酰肝素 鉴定了以高亲和力结合血小板反应蛋白的蛋白聚糖 在两种黑素瘤细胞系中（Cancer Res.48：6875，1988）。 一个不寻常 硫酸化糖脂仅存在于黑色素瘤细胞系中， 血小板反应蛋白与血小板反应蛋白结合并介导黑色素瘤细胞 spreading（同上）。为了进一步明确血小板反应蛋白的作用机制， 与肿瘤细胞的相互作用， 血小板反应蛋白正在被表征。 小细胞肺癌细胞 它们附着在血小板反应蛋白上，但不附着在其他粘附蛋白上， 用于鉴定特异性血小板反应蛋白受体。 细胞内 细胞对血小板反应蛋白结合的反应， 受体也在研究中。 血小板反应蛋白mRNA表达 研究人员正在检查肿瘤细胞， 凝血酶敏感蛋白合成与体内转移潜能。