Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability
Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability
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DOI：
10.1016/j.bbrc.2005.06.010
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发表时间：
2005-08-05
影响因子：
3.1
通讯作者：
Ochiai, A
中科院分区：
文献类型：
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作者：
Nakamura, M;Miyamoto, S;Ochiai, A
胰岛素样生长因子结合蛋白(IGFBPs)的蛋白水解性修饰在调节胰岛素样生长因子(IGF)的生物利用度方面具有重要的生理作用。最近，我们证实了多种肿瘤细胞产生的基质金属蛋白酶-7/基质溶素在体外催化IGFBP-3的蛋白分解，调节IGF的生物利用度，从而对非贴壁培养产生抗细胞凋亡的作用。在本研究中，我们研究了基质金属蛋白酶-7是否有助于其他五种IGFBP-1、IGFBP-2、IGFBP-4、IGFBP-5和IGFBP-6的蛋白分解，以及这是否导致I型胰岛素样生长因子受体(IGF-1R)的磷酸化。MMP7可切割所有6种IGFBPs，导致IGF介导的IGF-1R磷酸化，该作用可被EDTA抑制。这些结果表明，肿瘤细胞来源的基质金属蛋白酶-7可以调节肿瘤周围微环境中IGF的生物利用度，在肿瘤周围发现了各种IGF/IGFBP复合体，从而有利于肿瘤细胞在侵袭和转移过程中的生长和生存。(C)2005 Elsevier Inc.保留所有权利。
Proteolytic modification of insulin-like growth factor binding proteins (IGFBPs) plays an important physiological role in regulating insulin-like growth factor (IGF) bioavailability. Recently, we demonstrated that matrix metalloproteinase-7 (MMP-7)/Matrilysin produced by various cancer cells catalyzes the proteolysis of IGFBP-3 in vitro and regulates IGF bioavailability, resulting in an anti-apoptotic effect against anchorage-independent culture. In the present study, we investigated whether MMP-7 contributes to proteolysis of the other five IGFBPs, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6, and whether this results in phosphorylation of the IGF type I receptor (IGF-1R). MMP-7 cleaved all six IGFBPs, resulting in IGF-mediated IGF-1R phosphorylation, which was inhibited by EDTA treatment. These results suggest that MMP-7 derived from cancer cells can regulate IGF bioavailability in the microenvironment surrounding the tumor, where various kinds of IGF/IGFBP complexes are found, thereby favoring cancer cell growth and survival during the processes of invasion and metastasis. (c) 2005 Elsevier Inc. All rights reserved.