Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells
Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells
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DOI：
10.1677/jme.0.0320859
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发表时间：
2004-06-01
影响因子：
3.5
通讯作者：
Elmlinger, MW
中科院分区：
文献类型：
--
作者：
Schütt, BS;Langkamp, M;Elmlinger, MW
胰岛素样生长因子结合蛋白（IGFBP）-2的肿瘤性产生通常与肿瘤的恶性程度和侵袭性相关。由于IGFBP-2在其C-末端含有RGD基序，因此假设该蛋白质可独立于IGF通过整联蛋白作用于肿瘤细胞。为了研究这一点，在两种肿瘤细胞系中检查了整合素结合、细胞内信号传导以及IGFBP-2对细胞粘附和增殖的影响。在示踪剂置换研究中，高达30%的添加的I-125-hIGFBP-2特异性结合细胞。结合的I-125-hIGFBP-2可被IGFBP-2、IGFBP-1和RGD-（Gly-Arg-Asp）肽可逆置换，但不被IGFBP-3、-4、-5、-6和RGE-（Gly-Arg-Glu）-coritaining肽置换。用针对不同整联蛋白的抗体和用纤连蛋白阻断证实IGFBP-2细胞表面结合对α 5 β 1-整联蛋白是特异性的。IGFBP-2与等摩尔量的IGF-I和IGF-II孵育消除了RGD特异性结合。IGFBP-2在细胞表面的结合导致粘着斑激酶（FAK）的去磷酸化高达37%（P
The neoplastic production of the insulin-like growth factor binding protein (IGFBP)-2 often correlates with tumor malignancy and aggressiveness. Since IGFBP-2 contains an RGD motif in its C-terminus, it was hypothesized that this protein may act independently of IGF on tumor cells through integrins. To investigate this, integrin binding, intracellular signaling and the impact of IGFBP-2 on cell adhesion and proliferation were examined in two tumor cell lines. In tracer displacement studies, up to 30% of the added I-125-hIGFBP-2 specifically bound to the cells. Bound I-125-hIGFBP-2 was reversibly displaced by IGFBP-2, IGFBP-1 and RGD-(Gly-Arg-Asp)-containing peptides, but not by IGFBP-3, -4, -5, -6 and RGE-(Gly-Arg-Glu)-coritaining peptides. Blocking with antibodies directed against different integrins and with fibronectin demonstrated that IGFBP-2 cell surface binding is specific for alpha5beta1-integrin. Incubation of IGFBP-2 with equimolar quantities of IGF-I and IGF-II annihilated RGD-specific binding. IGFBP-2 binding at the cell surface led to dephosphorylation of the focal adhesion-kinase (FAK) of up to 37% (P