Mohnike K, Kluba U, Blum W F, Aumann V, Vorwerk P, Mittler U
Zentrum für Kinderheilkunde, Otto-von-Guericke-Universität Magdeburg.
Klin Padiatr. 1995 Jul-Aug;207(4):225-9. doi: 10.1055/s-2008-1046545.
The IGF regulatory system has been shown to mediate mitogenic effects during normal growth and tumor proliferation. The bioavailability of both IGF-I and IGF-II is regulated by at least six specific IGF binding proteins (IGFBPs). Whereas IGFBP-3 is the main IGFBP postnatally, IGFBP-2 is the predominant IGFBP during fetal life. In addition, IGFBP-2 is expressed in a range of tumor cell lines. In order to investigate the IGF regulatory pathway in malignancies we analyzed by RIA serum samples of 49 children with leukemia, Non-Hodgkins' Lymphoma (NHL) or solid tumors at the time of diagnosis. Serum concentrations of IGF-I (mean/range: -2.4/0.3 to -9.9 SDS), IGF-II (-2.5/0.2 to -5.6 SDS) and IGFBP-3 (-1.3/2.2 to -6.8 SDS) were significantly decreased, but IGFBP-2 (3.2/-0.9 to 8.6 SDS) was elevated. Both absolute as well as SDS values of IGF-I, -II and the sum of IGF-I and IGF-II (r = -0.49, p < 0.01) were inversely correlated with IGFBP-2. Serum levels of the growth factors IGF-I and IGF-II were significantly decreased in different types of malignancies to concentrations usually seen only in patients with growth hormone deficiency or during starvation. However, the elevated levels of IGFBP-2 in 70% of our patients exceeded by far those in growth hormone deficiency. Furthermore, in this study we could demonstrate that serum levels of IGF-I and IGF-II were inversely correlated to IGFBP-2 independent on the type of malignancy, indicating a common regulatory mechanism of the IGF signaling pathway in these diseases.
胰岛素样生长因子（IGF）调节系统已被证明在正常生长和肿瘤增殖过程中介导促有丝分裂作用。IGF-I和IGF-II的生物利用度受至少六种特定的IGF结合蛋白（IGFBPs）调节。出生后IGFBP-3是主要的IGFBP，而在胎儿期IGFBP-2是主要的IGFBP。此外，IGFBP-2在一系列肿瘤细胞系中表达。为了研究恶性肿瘤中的IGF调节途径，我们通过放射免疫分析（RIA）对49例白血病、非霍奇金淋巴瘤（NHL）或实体瘤患儿诊断时的血清样本进行了分析。IGF-I（平均值/范围：-2.4/0.3至-9.9 SDS）、IGF-II（-2.5/0.2至-5.6 SDS）和IGFBP-3（-1.3/2.2至-6.8 SDS）的血清浓度显著降低，但IGFBP-2（3.2/-0.9至8.6 SDS）升高。IGF-I、-II以及IGF-I和IGF-II之和的绝对值和SDS值（r = -0.49，p < 0.01）均与IGFBP-2呈负相关。在不同类型的恶性肿瘤中，生长因子IGF-I和IGF-II的血清水平显著降低至通常仅在生长激素缺乏患者或饥饿期间才出现的浓度。然而，我们70%的患者中IGFBP-2水平的升高远远超过生长激素缺乏患者。此外，在本研究中我们可以证明，IGF-I和IGF-II的血清水平与IGFBP-2呈负相关，且与恶性肿瘤类型无关，表明这些疾病中IGF信号通路存在共同的调节机制。
