CELL INTERACTIONS WITH THROMBOSPONDIN

细胞与血小板反应蛋白的相互作用

• 批准号: 3752080
• 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/3752080
• 关键词: cell adhesion; cell adhesion molecules; cell cycle; cell growth regulation; cell migration; cell motility; gene expression; glycolipids; glycoproteins; human tissue; melanoma; metastasis; molecular site; neoplastic cell; protein sequence; protein structure function; receptor; receptor binding; synthetic peptide; thrombospondins; tissue /cell culture; transforming growth factors; vascular endothelium

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 that 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;l988:6875). 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. Synthetic peptides from this region of thrombospondin are being used to define the sites recognized by thrombospondin receptors. The intracellular responses of cells to binding of thrombospondin to 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.

凝血酶反应蛋白在细胞黏附、迁移和肿瘤中的作用 转移情况正在调查中。我们已经确定了两个区域 介导黏附和迁移反应的凝血酶反应蛋白分子 培养的人黑色素瘤细胞对凝血酶敏感蛋白。羧基末端 结构域介导附着和触觉趋化，而氨基末端结构域 调节细胞扩散和趋化作用。细胞受体识别 凝血酶原蛋白的这两个区域正在研究中。一类 受体是与氨基末端结合的硫化糖偶联物。 凝血酶原蛋白结构域。一种少量的硫酸乙酰肝素蛋白多糖，可结合 在两个黑色素瘤细胞中鉴定出高亲和力的凝血酶反应蛋白 LINES(癌症研究报告48；1988：6875)。一种不同寻常的硫化糖脂 仅在通过凝血酶敏感蛋白结合的黑色素瘤细胞系中 凝血酶原蛋白和介导黑色素瘤细胞扩散(同上)。为了进一步 明确凝血酶反应蛋白与肿瘤细胞相互作用的机制， 凝血酶反应蛋白羧基末端的受体正在被 特色化的。来自凝血酶反应蛋白这一区域的合成肽 被用来定义凝血酶反应蛋白受体识别的部位。 细胞对凝血酶敏感蛋白结合的细胞内反应 两种类型的受体也在研究中。的表达 正在检测肿瘤细胞中的凝血酶反应蛋白mRNA，以寻找 凝血酶反应蛋白的合成与体内转移潜能的关系。