Wu Zhiliang, Boonmars Thidarut, Nagano Isao, Boonjaraspinyo Sirintip, Pinlaor Somchai, Pairojkul Chawalit, Chamgramol Yaovalux, Takahashi Yuzo
Department of Parasitology, Gifu University Graduate School of Medicine, Yanagido1-1, Gifu 501-1194, Japan.
Tumour Biol. 2012 Aug;33(4):1169-78. doi: 10.1007/s13277-012-0360-0. Epub 2012 Feb 29.
Galectin-1 is a beta-galactoside-binding lectin to function in cell adhesion, proliferation, differentiation, and might be involved in tumor progression and metastasis. In the present study, the expression kinetics of galectin-1 during the tumorigenesis of a parasite Opisthorchis viverrini infection-induced cholangiocarcinoma (CCA) was investigated in model animal hamsters, and the expression was confirmed in human CCA cases. It was found that galectin-1 was overexpressed at mRNA and protein levels with the tumor progression. The mRNA expression was elevated in very early stage during tumorigenesis and the increase was time dependent. Galectin-1 protein expression profiles indicated that the increased expression was mainly located in the epithelium of extensively proliferated and hyperplasia small bile ducts at early stage of CCA development in model animal and mainly in the extensive tumor stroma tissues in both model animals and human CCA cases at later stage. The analysis of correlation of the overexpression with clinicopathology in human cases suggested that high expression of galectin-1 was associated with advanced stage and metastasis and with shorter cumulative overall survival of the patients. Multivariate Cox regression analysis revealed that galectin-1 expression was of independent prognostic significance for CCA. Our results suggest that galectin-1 is likely involved in the tumorigenesis and expected to serve as a tumor stroma marker in diagnosis and prediction of metastasis and poor prognosis of the opisthorchiasis-associated CCA.
半乳糖凝集素-1是一种β-半乳糖苷结合凝集素,具有细胞黏附、增殖、分化功能,可能参与肿瘤进展和转移。在本研究中,在模型动物仓鼠中研究了寄生虫华支睾吸虫感染诱导的胆管癌(CCA)肿瘤发生过程中半乳糖凝集素-1的表达动力学,并在人类CCA病例中得到证实。研究发现,随着肿瘤进展,半乳糖凝集素-1在mRNA和蛋白质水平均过度表达。在肿瘤发生的极早期,mRNA表达升高,且这种增加呈时间依赖性。半乳糖凝集素-1蛋白表达谱表明,在模型动物CCA发展早期,表达增加主要位于广泛增殖和增生的小胆管上皮,而在模型动物和人类CCA病例的后期,主要位于广泛的肿瘤基质组织。对人类病例中过表达与临床病理相关性的分析表明,半乳糖凝集素-1的高表达与晚期和转移相关,与患者较短的累积总生存期相关。多因素Cox回归分析显示,半乳糖凝集素-1表达对CCA具有独立的预后意义。我们的结果表明,半乳糖凝集素-1可能参与肿瘤发生,有望作为华支睾吸虫病相关CCA转移和预后不良诊断及预测的肿瘤基质标志物。