【背景知识】 在人体系统中,胰岛素样生长因子 (IGF) 在各种组织和细胞类型中调节增殖、分化、凋亡、细胞粘附和代谢。 IGFBP-2 是一种 31.3 kDa 的未糖基化多肽,可形成 IGF 二元复合物,没有昼夜节律。在空腹、创伤和大手术后,其在血液中的浓度会增加,但在恶性疾病的情况下最为强烈。 在各种肿瘤类型(5-10)中,IGFBP-2随着进展程度严格增加,并在缓解期恢复正常值。在 GHI 治疗下,IGFBP-2 浓度降低,例如在 18 三体中,母体血清 iGFBP-2 降低,lGFBP-1 升高;因此,IGFBP-2/IGFBP-1 比率是这方面的标志 (17)。 转基因生物是研究基因/蛋白质功能的好机会。小鼠/大鼠模型代表了进一步研究 IGFBP-2 在生理和病理过程中的重要性的合适系统。因此,小鼠中 IGFBP-2' 基因的过表达导致出生后体重增加减少 (18) 和脾脏重量减少 30%。然而,所有其他器官仅显示适度的体重减轻。然而,lIGFBP-2 对生物体的影响可以通过改变其他 lIGF 结合蛋白的表达来补偿。尤其是在研究 在肿瘤生物学中,小鼠/大鼠系统可以具有系统研究模型的特征。使用 IGFBP-2 转染的肾上腺皮质肿瘤细胞的例子可以通过显着增加的方式显示对肿瘤细胞生理的影响。过氧化氢酶活性 (19). IGFBP-2 还通过 RGD 氨基酸基序肿瘤细胞相互作用,例如,可以刺激神经胶质瘤细胞的侵袭 (20)。 参考文献: 1.ElImlinger MW,Wimmer K, Biemer E, Blum WF, Ranke MB, Dannecker GE,(1996) Insulin-like growth factorbinding protein 2 is differentially expressed in leukaemic T-and B-cell lines. Growth Regulation 6,152-157 2.Hoeflich A, Nedbal S, Blum WF, Erhard M, Lahm H,Brem G, Kolb HJ,Wanke R, Wolf E.(2001)Growthinhibition in giant growth hormone transgenic mice by overexpression of insulin-like growth factor-bindingprotein-2. Endocrinology 142:1889-98 3.Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, Wollmann HA(2000) Significanceof basal lGF-J,IGFBP-3 and lGFBP-2 measurements in the diagnostics of short stature in children.HormoneResearch 54:60-68 4.Ranke MB, Schweizer R, EImlinger MW, Weber K, Binder G, Schwarze CP, Wollmann HA (2001).Relevanceof IGF-l,IGFBP-3, and IGFBP-2 measurements during GH treatment of GH-deficient and non-GH-deficientchildren and adolescents.Hormone Research 55:115-124 5.Crofton PM,Ahmed SF, Wade JC, EImlinger MW, Ranke MB, Kelnar CJH, Wallace WHB (1999)Effects of a,third intensification block of chemotherapy on bone and collagen turnover,insulin-like growth factor , itsbinding proteins and short term growth in children with acute lymphoblastic leukemia. European Joumal ofCancer 35: 960-967 6.Muller HL, Oh Y, Lehmbecher T, Blum WF, Rosenfeld RG.(1994) Insulin-like growth factor-binding protein-2concentrations in cerebrospinal fluid and serum of children with malignant solid tumors or acute leukemia.JClin Endocrinol Metab.79: 428-34 7.Martin W EImlinger,Martin H Deininger, Burkhardt S Schuett,Richard Meyemann, Frank Duffner,Enst HGrote, and Michael B Ranke (2o01) in vivo expression of the insulin-like growth factor binding protein-2 inhuman gliomas increases with the tumor grade. Endocrinology 142:1652-1658 8.Cohen P, Peehl DM, Stamey TA,Wilson KF,Clemmons DR, Rosenfeld RG (1993)Elevated levels of insulin-like growth factor-binding protein-2 in the serum of prostate cancer patients.i Clin Endocrinol Metab.76:1031-1035 9.Boulle N,Baudin E, Gicquel C, Logie A, Bertherat J , Penfornis A, Bertagna X, Luton JP, Schlumberger M, LeBouc Y.(2001)Evaluation of plasma insulin-ike growth factor binding protein-2 as a marker for adrenocorticaltumors.Eur J Endocrinol.144: 29-36 10.Ranke MB,Maier KP, Schweizer R, Stadler B, Schlecher s,Elmlinger MW,Flehmig B (2003), Pilot study ofelevated levels of insulin-like growth factor-binding protein-2 as indicators of hepatocellular carcinoma. HormRes 60:174-180 11.Rosenfeld RG,Roberts CT Jr. (eds.) (1999) The lGF system:Contemporary Endocrinology Series; HumanaPress 12.Jones Jl,Clemmons DR.(1995) Insulin-like growth factors and their binding proteins: biological actions.Endocr Rev.16:3-34 13.Chard T (1994) Insulin-like growth factors and their binding proteins in normal and abnormal foetal growth.Growth Reg 4: 91-100 14.Ranke MB,EImlinger Mw (1997) Functional role of insulin-like growth factor binding proteins. HormoneResearch 48 (suppl 4): 9-15 15.EImlinger MW, Bell M,Schitt,BS, Langkamp M, KutohE, Ranke MB (2001) Transactivation of the lGFBP-2promoter in human tumor cell lines.Molecular and Cellular Endocrinology 175:211-218 16.Hoeflich A,Reisinger R, Lahim H, Kiess W, Blum WF, Kolb HuJ, Weber MM,Wolf E.(2001) Insulin-ike growthfactor-binding protein 2 in tumorigenesis: protector or promoter? Cancer Res.15:8601-8610 17.Miell JP, Langford KS, Jones JS,Noble P, Westwood M,White A, Nicolaides KH.(1997) The maternalinsulin-like growth factor (IGF) and lGF-binding protein response to trisomic pregnancy during the firsttrimester a possible diagnostic tool for trisomy 18 pregnancies.J Clin Endocrinol Metab.82:287-292 18.Hoeflich A, wu M,Mohan S,Foll J, Wanke R, Froehlich T,Amnold GJ, Lahm H, Kolb HJ,Wolf E. (1999)Qverexpression of insulin-like growth factor-binding protein-2 in transgenic mice reduces postnatal bodyweight gain.Endocrinology 140(12):5488-5496. 19.Hoeflich A, Fettscher O,Preta G, Lahm H, Kolb HJ, Wolf E, Weber MM(2003) Ilncreased activity of catalasein tumor cells overexpressing IGFBP-2.Horm Metab Res 35(11-12):816-821. 20Song sw, Fuller GN, Khan A, Kong S, Shen W, Taylor E, Ramdas L, Lang FF, zhang w.(2003) lip45, aninsulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation ofglioma cell invasion. Proc Natl Acad Sci USA 100(24):13970-13975.