Induction of fibronectin matrix assembly in human fibrosarcoma cells by dexamethasone.
Induction of fibronectin matrix assembly in human fibrosarcoma cells by dexamethasone.
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DOI：
10.1083/jcb.104.3.601
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发表时间：
1987-03
影响因子：
7.8
通讯作者：
Etzler, C A
中科院分区：
文献类型：
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作者：
McKeown-Longo, P J;Etzler, C A
先前的研究已经表明，纤连蛋白组装到培养的成纤维细胞的细胞外基质中是由特异性基质组装受体介导的，所述特异性基质组装受体识别纤连蛋白分子的氨基末端中的结合位点（McKeown-Longo，P. J.，和D.F. Mosher，1985，J. Cell Biol.，100：364-374）。在地塞米松的存在下，人纤维肉瘤细胞（HT-1080）获得的能力，特异性结合外源性血浆纤连蛋白，并将其纳入洗涤剂不溶性细胞外基质。地塞米松诱导的纤维连接蛋白与HT-1080细胞的结合呈时间依赖性、剂量依赖性，并被放线菌酮抑制。饱和结合曲线表明地塞米松诱导每个细胞出现7.7 × 10（4）个基质组装受体。诱导受体对可溶性纤连蛋白的解离常数（KD）为5.0 × 10 ~（-8）M。在平行实验中，正常成纤维细胞显示每个细胞4.1 × 10（5）个受体（KD = 5.3 × 10（-8）M）。在放线菌酮的存在下，诱导的HT-1080细胞上的纤连蛋白结合活性在12小时内恢复到未诱导的水平。相反，正常成纤维细胞上的纤连蛋白结合活性在放线菌酮存在下稳定长达54小时。受体结合的纤连蛋白转移到细胞外基质的一级速率常数（Kt = 2.07 × 10（-4）min-1）比正常成纤维细胞的一级速率常数（Kt = 1.32 × 10（-3）min-1）小4 ~ 5倍。乳过氧化物酶催化的HT-1080单细胞膜碘化反应表明地塞米松增强了48，000-mol-wt的细胞表面蛋白.这些实验的结果表明，地塞米松诱导HT-1080细胞表面的功能性基质组装受体;然而，纤连蛋白掺入基质的速率比正常成纤维细胞慢得多。
Previous studies have suggested that the assembly of fibronectin into the extracellular matrix of cultured fibroblasts is mediated by specific matrix assembly receptors that recognize a binding site in the amino terminus of the fibronectin molecule (McKeown-Longo, P.J., and D.F. Mosher, 1985, J. Cell Biol., 100:364-374). In the presence of dexamethasone, human fibrosarcoma cells (HT-1080) acquired the ability to specifically bind exogenous plasma fibronectin and incorporate it into a detergent-insoluble extracellular matrix. Dexamethasone-induced fibronectin binding to HT-1080 cells was time dependent, dose dependent, and inhibited by cycloheximide. Saturation binding curves indicated that dexamethasone induced the appearance of 7.7 X 10(4) matrix assembly receptors per cell. The induced receptors exhibited a dissociation constant (KD) for soluble fibronectin of 5.0 X 10(-8) M. In parallel experiments, normal fibroblasts exhibited 4.1 X 10(5) receptors (KD = 5.3 X 10(-8) M) per cell. In the presence of cycloheximide, the induced fibronectin-binding activity on HT-1080 cells returned to uninduced levels within 12 h. In contrast, fibronectin-binding activity on normal fibroblasts was stable in the presence of cycloheximide for up to 54 h. The first-order rate constant (Kt = 2.07 X 10(-4) min-1) for the transfer of receptor-bound fibronectin to extracellular matrix was four- to fivefold less than that for normal fibroblasts (Kt = 1.32 X 10(-3) min-1). Lactoperoxidase- catalyzed iodination of HT-1080 monolayers indicated that a 48,000-mol- wt cell surface protein was enhanced with dexamethasone. The results from these experiments suggest that dexamethasone induces functional matrix assembly receptors on the surface of HT-1080 cells; however, the rate of incorporation of fibronectin into the matrix is much slower than that of normal fibroblasts.