Oh Y
Department of Pediatrics, Oregon Health Sciences University, Portland 97201, USA.
Breast Cancer Res Treat. 1998 Feb;47(3):283-93. doi: 10.1023/a:1005911319432.
The human IGFBP family consists of at least seven proteins, designated as IGFBP-1, -2, -3, -4, -5, -6, and-7. IGFBPs 1-6 bind IGF-I and IGF-II with high affinity whereas IGFBP-7, a newly identified IGFBP, binds IGFs with lower affinity and constitutes a low-affinity member of the IGFBP family. IGFBPs serve to transport the IGFs, prolong their half-lives, and modulate their biological action. At the cellular level, IGFBPs can either potentiate or inhibit the mitogenic effects of IGFs, depending upon cell types and IGFBP species (IGF-dependent action of IGFBPs). However, recent studies have indicated that IGFBPs, especially IGFBP-3, potently inhibit breast cancer cell growth in an IGF-independent manner. The IGF-independent action of IGFBP-3 requires interaction with cell-surface association proteins, presumably putative IGFBP-3 specific receptors, and is responsible for growth inhibitory action of the known growth suppressing factors such as TGF-beta, retinoic acid, and antiestrogens in breast cancer cells. Thus, IGFBP-3 appears to be a major factor in a negative control system involved in regulating human breast cancer cell growth in vitro. IGFBP-7, representing a low affinity IGFBP, appears to function as an IGF-independent cell growth regulator in breast cancer cells. Overall structural similarity between IGFBP-7 and classical high affinity IGFBPs 1-6 suggests that the mechanisms of action and signaling pathways used by IGFBP-7 may provide insight into the IGF-independent actions of the high affinity IGFBPs. A fuller understanding of the IGF-independent action of IGFBPs will allow us to understand how the growth of neoplastic cells can be modulated by the IGF/IGFBP system, and how other growth factors or pharmacological agents can interface with this system.
人类胰岛素样生长因子结合蛋白（IGFBP）家族至少由七种蛋白质组成，分别命名为IGFBP - 1、- 2、- 3、- 4、- 5、- 6和- 7。IGFBP - 1至- 6以高亲和力结合胰岛素样生长因子 - I（IGF - I）和胰岛素样生长因子 - II（IGF - II），而新发现的IGFBP - 7则以较低亲和力结合IGF，是IGFBP家族的低亲和力成员。IGFBP起到转运IGF、延长其半衰期并调节其生物学作用的功能。在细胞水平上，IGFBP根据细胞类型和IGFBP种类，既可以增强也可以抑制IGF的促有丝分裂作用（IGFBP的IGF依赖性作用）。然而，最近的研究表明，IGFBP，尤其是IGFBP - 3，能以不依赖IGF的方式有效抑制乳腺癌细胞的生长。IGFBP - 3的不依赖IGF作用需要与细胞表面相关蛋白相互作用，推测可能是假定的IGFBP - 3特异性受体，并且与乳腺癌细胞中已知生长抑制因子如转化生长因子 - β（TGF - β）、视黄酸和抗雌激素的生长抑制作用有关。因此，IGFBP - 3似乎是体外调节人类乳腺癌细胞生长的负控制系统中的一个主要因素。IGFBP - 7作为一种低亲和力IGFBP，似乎在乳腺癌细胞中作为不依赖IGF的细胞生长调节因子发挥作用。IGFBP - 7与经典的高亲和力IGFBP - 1至- 6之间的整体结构相似性表明，IGFBP - 7所使用的作用机制和信号通路可能有助于深入了解高亲和力IGFBP的不依赖IGF作用。对IGFBP不依赖IGF作用的更全面理解将使我们能够了解IGF / IGFBP系统如何调节肿瘤细胞的生长，以及其他生长因子或药物如何与该系统相互作用。
