Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6
Binding characteristics of pro-insulin-like growth factor-II from cancer patients: binary and ternary complex formation with IGF binding proteins-1 to -6
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DOI：
10.1677/joe.0.1650253
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发表时间：
2000-05-01
影响因子：
4
通讯作者：
Baxter, RC
中科院分区：
文献类型：
--
作者：
Bond, JJ;Meka, S;Baxter, RC
许多谣言分泌IGF-II在不完全加工的前体形式。这些pro-IGF-II形式与六种IGF结合蛋白（IGFBPs）复合的能力知之甚少。在这项研究中，pro-IGF-II已从两名非胰岛细胞肿瘤低血糖患者的血清和肿瘤组织中提取。这些样品用于研究二元复合物的形成与IGFBPs-1至-6使用竞争性IGF-II结合试验和三元复合物的形成与IGFBP-3和IGFBP-5。在每种情况下，IGFBPs-1至-6显示出很少的差异，在其形成二元复合物的能力与重组IGF-II或肿瘤衍生的pro-IGF-II形式，根据IGF-II免疫反应性的制剂进行标准化。如前所述，与成熟IGF-II的复合物形成相比，酸不稳定亚基（ALS）与IGFBP-3和pro-IGF-II的三元复合物形成大大减少。与此相反，ALS绑定类似IGFBP-5的pro-IGF-II和成熟的IGF-II的存在下。这些研究表明，pro-IGF-II优先形成二元复合物与IGFBP-5，和三元复合物与IGFBP-5，而不是三元复合物与IGFBP-3，主要是在正常血清中看到的。这可能会增加血清pro-IGF-II的组织利用率，使其胰岛素样潜力得以实现。
Many rumours secrete IGF-II in incompletely processed precursor forms. The ability of these pro-IGF-II forms to complex with the six IGF binding proteins (IGFBPs) is poorly understood. In this study, pro-IGF-II has been extracted from the serum and tumour tissue of two patients with non-islet cell tumour hypoglycaemia. These samples were used to study binary complex formation with IGFBPs-1 to -6 using competitive IGF-II binding assays and ternary complex formation with IGFBP-3 and IGFBP-5.In each case, IGFBPs-1 to -6 showed little difference in their ability to form binary complexes with recombinant IGF-II or tumour-derived pro-IGF-II forms, when the preparations were standardised according to IGF-II immunoreactivity. As previously described, ternary complex formation by acid-labile subunit (ALS) with IGFBP-3 and pro-IGF-II was greatly decreased compared with complex formation with mature IGF-II. In contrast, ALS bound similarly to IGFBP-5 in the presence of pro-IGF-II and mature IGF-II.These studies suggest that pro-IGF-II preferentially forms binary complexes with IGFBPs, and ternary complexes with IGFBP-5, rather than ternary complexes with IGFBP-3 as seen predominantly in normal serum. This may increase the tissue availability of serum pro-IGF-II, allowing its insulin-like potential to be realised.