Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma
Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma
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DOI：
10.1093/carcin/bgl247
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发表时间：
2007-05-01
期刊：
影响因子：
4.7
通讯作者：
Imai, Kohzoh
中科院分区：
文献类型：
--
作者：
Imsumran, Arisa;Adachi, Yasushi;Imai, Kohzoh
胰岛素样生长因子（IGF）-I受体（IGF-Ir）信号传导是许多肿瘤的致瘤性和进展所必需的，但该途径尚未作为食管鳞状细胞癌（ESCC）的预后因素或潜在治疗靶点进行充分研究。本文应用免疫组化方法研究了100例手术切除的食管鳞癌组织中IGF-Ir和IGF-II配体的表达与预后的关系。然后，我们评估了在体外使用显性负性IGF-Ir（IGF-Ir/dn）阻断IGF受体信号传导在ESCC中的治疗效果。IGF-Ir和IGF-II的表达分别在60%和50%的肿瘤中检测到，并且与浸润深度、转移、晚期肿瘤分期和复发相关。在单因素和多因素分析中，肿瘤同时表达IGF-Ir和IGF-II的患者的生存期明显短于单独表达或均不表达的患者。IGF-Ir/dn通过阻断配体诱导的Akt激活抑制增殖和运动，以及上调化疗诱导的凋亡。我们建议，IGF-Ir/IGF-II在ESCC中的检测可能有助于预测复发和预后不良，并为IGF-Ir靶向治疗选择患者。IGF-Ir的治疗性阻断可能是ESCC的有用的抗癌治疗。
Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for tumorigenicity and progression of many tumors but this pathway has not been well studied as a prognostic factor or potential therapeutic target in esophageal squamous cell carcinoma (ESCC). In this paper, the association between the expression of IGF-Ir and IGF-II ligand and prognosis was investigated immunohistochemically in 100 surgically resected ESCC. We then assessed the therapeutic effect of blocking IGF receptor signaling using dominant negative IGF-Ir (IGF-Ir/dn) in ESCC in vitro. Expression of IGF-Ir and IGF-II were detected in 60 and 50% of tumors, respectively, and were associated with invasion depth, metastasis, advanced tumor stage and recurrence. Patients with tumors expressing both IGF-Ir and IGF-II had a significantly shorter survival than those expressing either alone or neither in both single and multivariate analysis. IGF-Ir/dn suppressed proliferation and motility as well as upregulating chemotherapy-induced apoptosis through blocking ligand-induced Akt activation. We propose that detection of IGF-Ir/IGF-II in ESCC may be useful for the prediction of recurrence and poor prognosis and for selecting patients for IGF-Ir-targeted therapy. Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC.