CELL INTERACTIONS WITH THROMBOSPONDIN

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 介导细胞扩散和趋化性。 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， 凝血酶敏感蛋白结构域。 一种次要的硫酸乙酰肝素蛋白聚糖， 在两个黑色素瘤细胞系中鉴定出具有高亲和力的血小板反应蛋白 （Cancer Res 48; 1988：6875）。 一种不寻常的硫酸化糖脂，仅存在于 在血小板反应蛋白上扩散的黑素瘤细胞系与血小板反应蛋白结合 并介导黑素瘤细胞扩散（同上）。 以进一步限定 血小板反应蛋白与肿瘤细胞相互作用的机制， 血小板反应蛋白的羧基末端正在被表征。 合成 来自血小板反应蛋白这一区域的肽被用于定义 由血小板反应蛋白受体识别的位点。 细胞内反应 细胞对血小板反应蛋白与两种受体结合的反应， 也在调查中。 血小板反应蛋白mRNA在肿瘤细胞中的表达 正在研究血小板反应蛋白的合成与 体内转移潜能。

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;1988:6875). 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.