Pro-adhesive and chemotactic activities of thrombospondin-1 for breast carcinoma cells are mediated by α3β1 integrin and regulated by insulin-like growth factor-1 and CD98
Pro-adhesive and chemotactic activities of thrombospondin-1 for breast carcinoma cells are mediated by α3β1 integrin and regulated by insulin-like growth factor-1 and CD98
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DOI：
10.1074/jbc.274.16.11408
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发表时间：
1999-04-16
影响因子：
4.8
通讯作者：
Roberts, DD
中科院分区：
文献类型：
--
作者：
Chandrasekaran, S;Guo, NH;Roberts, DD
血小板反应蛋白-1（TSP 1）是一种具有促粘附和抗粘附活性的基质细胞蛋白。与硫酸化糖缀合物的结合介导可溶性TSP 1与MDA-MB-435细胞的最高亲和力结合，但这些细胞在固定的TSP 1上的附着和铺展主要是β（1）整联蛋白依赖性的。整合素α（3）β（1）是乳腺癌细胞粘附和趋化TSP 1的主要介质。这种整合素在MDA-MB-435细胞中部分有活性，但在MDA-MB-231和MCF-7细胞中大部分无活性，这需要β（1）整合素活化以诱导在TSP 1上的扩散。整合素介导的细胞在TSP 1上的铺展伴随着含有β 1整合素的丝状伪足的延伸。α（3）β（1）整联蛋白的TSP 1结合活性不受来自TSP 1的CD 47结合肽或蛋白激酶C激活的刺激，所述肽或蛋白激酶C激活在相同细胞中激活α（v）β（3）整联蛋白功能。在MDA-MB-231而不是MDA-MB-435细胞中，该整合素被百日咳毒素激活，而血清、胰岛素、胰岛素样生长因子-1和CD 98的连接增加了这两种细胞系中该整合素的活性。血清刺激伴随着CD 98的表面表达增加，而胰岛素样生长因子-1不增加CD 98的表达。因此，TSP 1对乳腺癌细胞的促粘附活性由调节α（3）β（1）整联蛋白活性的几种信号控制。
Thrombospondin-1 (TSP1) is a matricellular protein that displays both pro- and anti-adhesive activities. Binding to sulfated glycoconjugates mediates most high affinity binding of soluble TSP1 to MDA-MB-435 cells, but attachment and spreading of these cells on immobilized TSP1 is primarily beta(1) integrin-dependent. The integrin alpha(3)beta(1) is the major mediator of breast carcinoma cell adhesion and chemotaxis to TSP1. This integrin is partially active in MDA-MB-435 cells but is mostly inactive in MDA-MB-231 and MCF-7 cells, which require beta(1) integrin activation to induce spreading on TSP1. Integrin-mediated cell spreading on TSP1 is accompanied by extension of filopodia containing beta(1) integrins. TSP1 binding activity of the alpha(3)beta(1) integrin is not stimulated by CD47-binding peptides from TSP1 or by protein kinase C activation, which activate alpha(v)beta(3) integrin function in the same cells. In MDA-MB-231 but not MDA-MB-435 cells, this integrin is activated by pertussis toxin, whereas serum, insulin, insulin-like growth factor-1, and ligation of CD98 increase activity of this integrin in both cell lines. Serum stimulation is accompanied by increased surface expression of CD98, whereas insulinlike growth factor-1 does not increase CD98 expression. Thus, the pro-adhesive activity of TSP1 for breast carcinoma cells is controlled by several signals that regulate activity of the alpha(3)beta(1) integrin.