An evaluation of the role of insulin-like growth factors (IGF) and of type-I IGF receptor signalling in hepatocarcinogenesis and in the resistance of hepatocarcinoma cells against drug-induced apoptosis
An evaluation of the role of insulin-like growth factors (IGF) and of type-I IGF receptor signalling in hepatocarcinogenesis and in the resistance of hepatocarcinoma cells against drug-induced apoptosis
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DOI：
10.1016/j.bcp.2004.05.029
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发表时间：
2004-09-15
影响因子：
5.8
通讯作者：
Groyer, A
中科院分区：
文献类型：
--
作者：
Alexia, C;Fallot, G;Groyer, A
强有力的证据强调了胰岛素样生长因子（IGF）系统和I型IGF受体（IGF-IR）信号传导在肿瘤发生中的作用。在这方面：（i）IGF系统组分的表达模式的变化，IGF-I和-II的自分泌/旁分泌表达，IGF-IR的过表达，IGF结合蛋白（IGFBP）和II型IGF受体/阳离子非依赖性甘露糖-6-磷酸受体（IGF-II/M6 PR）的表达降低，和（ii）切割IGFBP的蛋白酶（例如，组织蛋白酶D）在肝细胞癌（HCC）患者、人肝癌细胞系及其条件培养基以及肝癌发生的啮齿动物模型中观察到。因此，用动物模型进行的研究确实表明IGF系统和IGF-IR信号传导可能在肝癌发生和HCC细胞的增殖和凋亡失调中起作用。最后，Raf/MEK/ERK（IGF-IR刺激的信号级联反应之一）在蒽环类药物诱导的HepG 2和Huh-7人肝癌细胞系凋亡中的作用强调了在设计抗肿瘤分子组合用于肿瘤治疗时必须小心。本文综述了IGF系统在原发性肝癌中的作用，特别关注其潜在的分子机制。在第二部分中，它强调了IGF-IR信号转导与化疗药物诱导的人肝癌细胞凋亡的假定干扰。(C)2004年爱思唯尔公司All rights reserved.
Strong evidence emphasizes the role of the insulin-like growth factor (IGF) system and of type-I IGF receptor (IGF-IR) signalling in tumourigenesis. In this connection: (i) changes in the expression pattern of components of the IGF system autocrine/paracrine expression of IGF-I and -II, overexpression of IGF-IR, decreased expression of IGF-binding proteins (IGFBPs) and of type-II IGF receptor/cation-independent mannose-6-phosphate receptor (IGF-II/M6PR) and (ii) increased serum concentrations of proteases that cleave the IGFBPs (e.g., cathepsin D) were observed in patients with hepatocellular carcinomas (HCC), in human hepatoma cell lines and in their conditioned culture medium, as well as in rodent models of hepatocarcinogenesis. Accordingly, studies carried out with animal models do suggest that the IGF system and IGF-IR signalling may play a role in hepatocarcinogenesis and in deregulated proliferation and apoptosis of HCC cells. Finally the instrumental role of Raf/MEK/ERK, one of the signalling cascades stimulated by IGF-IR, in anthracycline-induced apoptosis of HepG2 and Huh-7 human hepatoma cell lines emphasizes that care must be taken when designing combinations of antitumoural molecules for antineoplastic treatment. This review addresses the putative roles of the IGF system in primary HCC, with a special focus on the underlying molecular mechanisms. In a second part it emphasizes the putative interference of IGF-IR signalling with chemotherapeutic drug-induced apoptosis in human hepatoma cells. (C) 2004 Elsevier Inc. All rights reserved.