The roles of integrins and extracellular matrix proteins in the insulin-like growth factor I-stimulated chemotaxis of human breast cancer cells
The roles of integrins and extracellular matrix proteins in the insulin-like growth factor I-stimulated chemotaxis of human breast cancer cells
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DOI：
10.1074/jbc.271.5.2443
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发表时间：
1996-02-02
影响因子：
4.8
通讯作者：
Jones, JI
中科院分区：
文献类型：
--
作者：
Doerr, ME;Jones, JI
用改良的Boyden小室观察了胰岛素样生长因子I（IGF-I）对人乳腺癌细胞株MCF-7和MDA-231迁移的影响。10 ng/ml是刺激迁移的最佳IGF-I浓度，两种细胞类型中IGF-I刺激的迁移大多数是由于趋化性，MCF-7细胞不能在明胶或纤连蛋白包被的膜上迁移，并且仅少量在层粘连蛋白上迁移。相反，当使用玻连蛋白或IV型胶原包被的膜时，MCF-7细胞特异性地响应IGF-I而大量迁移，但不响应10%胎牛血清、表皮生长因子、成纤维细胞生长因子或血小板衍生生长因子-BB。IGF-I受体阻断抗体抑制IGF-I刺激的两种细胞类型的迁移，此外，α v β 5整合素的阻断抗体（一种玻连蛋白受体）通过玻连蛋白而不是通过IV型胶原蛋白抑制MCF-7细胞响应IGF-I的迁移。类似地，α 2和β 1整合素特异性阻断抗体显著抑制两种细胞类型通过IV型胶原包被膜的迁移，但不通过玻连蛋白。结论：1）IGF-I通过IGF-I受体促进这两种细胞的迁移; 2）玻连蛋白与α v β 5整联蛋白或胶原蛋白与α 2 β 1整联蛋白的相互作用对于MCF-7细胞中的完全IGF-I应答是必需的，和3）因为迁移代表转移扩散的体外模型，所以整联蛋白，细胞外基质蛋白和IGF-I可能在乳腺癌的体内转移中起协同作用。
The effects of insulin-like growth factor I (IGF-I) on the migration of two human breast cancer cell Lines, MCF-7 and MDA-231, were examined using a modified Boyden chamber. 10 ng/ml was the optimal IGF-I concentration for stimulation of migration, The majority of IGF-I-stimulated migration in both cell types was due to chemotaxis, MCF-7 cells failed to migrate on membranes coated with gelatin or fibronectin and migrated only in small numbers on laminin, In contrast, when vitronectin- or type IV collagen-coated membranes were used, the MCF-7 cells migrated in large numbers specifically in response to IGF-I but not to 10% fetal calf serum, epidermal growth factor, fibroblast growth factor, or platelet derived growth factor-BB. An IGF-I receptor-blocking antibody inhibited IGF-I-stimulated migration in both cell types, In addition, a blocking antibody to the alpha v beta 5 integrin (a vitronectin receptor) inhibited migration of MCF-7 cells in response to IGF-I through vitronectin but not through type IV collagen, Similarly, blocking antibodies specific for alpha 2 and beta 1 integrins significantly inhibited migration of both cell types through type IV collagen-coated membranes but not through vitronectin-coated membranes, We conclude that: 1) IGF-I stimulates migration of these two cell types through the IGF-I receptor; 2) interaction of vitronectin with the alpha v beta 5 integrin or collagen with the alpha 2 beta 1 integrin is necessary for the complete IGF-I response in MCF-7 cells, and 3) because migration represents an in vitro model for metastatic spread, integrins, extracellular matrix proteins, and IGF-I may play coordinated roles in the metastasis of breast cancer in vivo.