CELL INTERACTIONS WITH THROMBOSPONDIN

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 结构域调节附着和趋触性，而氨基末端 结构域介导细胞扩散和趋化作用。细胞受体 对凝血酶敏感蛋白这两个区域的认识正在研究中。 一类受体是硫酸盐化的糖偶联物，它与 凝血酶原蛋白的氨基末端结构域。少量硫酸乙酰肝素 鉴定出与凝血酶反应蛋白高亲和力结合的蛋白多糖 在两个黑色素瘤细胞系中(癌症研究48：6875,1988)。一种不同寻常的 硫酸糖脂只存在于黑色素瘤细胞系中 凝血酶敏感蛋白与凝血酶敏感蛋白结合并介导黑色素瘤细胞 传播(同上)。进一步明确凝血酶反应蛋白的作用机制 与肿瘤细胞的相互作用，羧基末端的受体 凝血酶敏感蛋白的特性正在研究中。小细胞肺癌细胞 它们附着在凝血酶原蛋白上，但不附着在其他黏附蛋白上 用于识别特定的凝血酶敏感蛋白受体。细胞内 细胞对凝血酶原蛋白在两种细胞上结合的反应 受体的研究也在进行中。凝血酶反应蛋白基因的表达 正在对肿瘤细胞进行检查以寻找与 凝血酶敏感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 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.