Fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent mechanism.

Fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent mechanism.
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纤连蛋白通过整合素依赖性机制抑制正常人黑色素细胞的凋亡。

DOI:
10.1111/1523-1747.ep12332650
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发表时间:
1997
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
Busacco,A
Busacco,A
中科院分区:
--
文献类型:
--
作者:
Scott,G;Cassidy,L;Busacco,A

文献摘要

被引文献

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最近的报道表明,细胞外基质的组分通过抑制细胞凋亡(程序性细胞死亡)作为细胞存活因子发挥作用。在这份报告中,我们表明,连接到纤连蛋白抑制正常人胎儿和新生儿黑素细胞的体外凋亡,并防止附着到底层基质或附着到多聚赖氨酸是黑素细胞凋亡的有效诱导剂。β1-阻断抗体增强附着于纤连蛋白的黑素细胞凋亡的能力,以及固定在固体支持物上的抗β1抗体抑制黑素细胞凋亡的能力,表明了β1-整联蛋白家族在介导细胞存活信号中的作用。细胞松弛素D逆转了纤连蛋白对黑素细胞凋亡的抑制作用,表明存活信号的转导需要完整的细胞骨架。人转移性黑色素瘤细胞系SKMEL 28在悬浮液中或在多聚赖氨酸上生长时,即使在不存在外源性生长因子的情况下培养4 d后,也对凋亡具有抗性。这些结果表明,纤连蛋白通过整合素依赖性途径抑制正常人黑素细胞的凋亡,并且在黑素细胞和黑色素瘤细胞中存在对凋亡的锚定依赖性调节的控制的显著差异。
Recent reports show that components of the extracellular matrix function as cell survival factors through the suppression of apoptosis (programmed cell death). In this report we show that attachment to fibronectin suppresses apoptosis of normal human fetal and neonatal melanocytesin vitroand that prevention of attachment to underlying matrix or attachment to poly-L-lysine is a potent inducer of apoptosis in melanocytes. A role for theβ1-integrin family in mediating cell survival signals was shown by the ability ofβ1-blocking antibodies to enhance apoptosis in melanocytes attached to fibronectin, and by the ability of anti-β1 antibodies immobilized on solid supports to suppress apoptosis in melanocytes. Cytochalasin D reversed the effect of fibronectin on the suppression of apoptosis in melanocytes, suggesting that an intact cytoskeleton is required for transduction of survival signals. A human metastatic melanoma cell line, SKMEL28, was resistant to apoptosis when grown in suspension or on poly-L-lysine, even after 4 d in culture in the absence of exogenous growth factors. These results suggest that fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent pathway and that significant differences in the control of anchorage-dependent regulation of apoptosis exist in melanocytes and melanoma cells.