Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin
Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin
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DOI：
10.1242/jcs.00097
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发表时间：
2002-11-15
影响因子：
4
通讯作者：
Holly, JMP
中科院分区：
文献类型：
--
作者：
McCaig, C;Perks, CM;Holly, JMP
胰岛素样生长因子结合蛋白（IGFBPs）对细胞功能具有非胰岛素样生长因子依赖的差异作用。我们研究了它们是否可以影响整合素受体介导的细胞附着到不同的细胞外基质（ECM）组分在Hs 578 T cells.Cell attachment到一个普通的ECM凝胶不受IGFBP-1和-6，但IGFBP-4和-5显着增加，IGFBP-2和-3减少。对于层粘连蛋白或IV型胶原蛋白的附着获得了类似的结果。然而，IGFBP-3增加了与纤维连接蛋白的附着，IGFBP-5降低了与纤维连接蛋白的附着。IGFBP-3和-5对细胞附着ECM的作用在含有可溶性Arg-Gly-Asp（RGD）的纤连蛋白片段的存在下丧失。血小板反应蛋白逆转了IGFBP-3对细胞粘附的作用，但IGFBP-5仍然增加了细胞粘附。在塑料上，IGFBP-3和IGFBP-5都不单独影响细胞活力;尽管神经酰胺诱导的细胞凋亡被IGFBP-3增强，但被IGFBP-5降低。RGD的存在逆转了IGFBP-5对细胞死亡的作用，但减弱了IGFBP-3的作用。当细胞在纤连蛋白上生长时，IGFBP-3的作用被逆转，它赋予细胞存活，而IGFBP-5的存活作用丧失。在每种情况下，纤连蛋白或纤连蛋白片段的存在决定了对细胞凋亡的易感性是增加还是减少。这些对细胞存活的影响被对整合素受体功能的急性影响所抵消; IGFBP-3和IGFBP-5能够在纤连蛋白存在下增强或抑制细胞附着。细胞存活受到来自ECM和生长因子（特别是IGFs）的信号的严格控制。我们的研究结果表明，除了作为IGF作用的重要调节剂之外，IGFBPs对细胞附着和存活具有直接作用，这些作用是特异性的并且依赖于存在的基质成分。
The insulin-like growth factor binding proteins (IGFBPs) have IGF-independent differential effects on cell function. We investigated whether they can affect integrin-receptor-mediated cell attachment to different extracellular matrix (ECM) components in Hs578T cells.Cell attachment to a general ECM gel was unaffected by IGFBP-1 and -6 but was significantly increased by IGFBP-4 and -5 and decreased by IGFBP-2 and -3. Similar results were obtained for attachment to laminin or collagen type IV. Attachment to fibronectin, however, was increased by IGFBP-3 and decreased by IGFBP-5. The actions of IGFBP-3 and -5 on cell attachment to ECM were lost in the presence of a soluble Arg-Gly-Asp (RGD)-containing fibronectin fragment. Thrombospondin reversed the actions of IGFBP-3 on cell attachment, but IGFBP-5 still increased cell attachment.On plastic, neither IGFBP-3 nor -5 alone affected cell viability; although ceramide-induced apoptosis was enhanced by IGFBP-3 but reduced by IGFBP-5. The presence of RGD reversed the action of IGFBP-5 on cell death but attenuated that of IGFBP-3. With cells grown on fibronectin, the action of IGFBP-3 was reversed, and it conferred cell survival, whereas the survival effect of IGFBP-5 was lost.In summary we have demonstrated that IGFBP-3 and 5 both have intrinsic effects on cell survival. In each case the presence of fibronectin or fibronectin fragments determines whether susceptibility to apoptosis is increased or decreased. These effects on cell survival are paralleled by acute effects on integrin receptor function; IGFBP-3 and -5 were able to either enhance or inhibit cell attachment in the presence of fibronectin. Cell survival is tightly controlled by cues from the ECM and from growth factors, particularly the IGFs. Our findings indicate that, in addition to being crucial modulators of IGF actions, the IGFBPs have direct actions on cell attachment and survival that are specific and dependent upon the matrix components present.