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半乳糖凝集素-1 是一种参与甲状腺癌进展的诊断标志物。

Galectin-1 is a diagnostic marker involved in thyroid cancer progression.

机构信息

Laboratory of Human Anatomy and Experimental Oncology, Faculty of Medicine and Pharmacy, University of Mons, Mons, Belgium.

Université Lille, Inserm, CHU Lille, UMR-S 1172 - JPARC - Jean-Pierre Aubert Research Center, F-59000 Lille, France.

出版信息

Int J Oncol. 2017 Sep;51(3):760-770. doi: 10.3892/ijo.2017.4065. Epub 2017 Jul 4.

Abstract

Fine-needle aspiration (FNA) is the most commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. Based on multifunctionality of the endogenous galectin-1, we aimed to assess its status for early diagnosis of thyroid cancer. Immunohistochemistry for galectin-1 and -3 was performed on a clinical series of 69 cases of thyroid lesions. Galectin-1 expression was further examined in two additional tissue microarrays (TMA) composed of 66 follicular adenomas and 66 papillary carcinomas in comparison to galectin-3 and cytokeratin-19 (CK19). In addition, a knockdown of galectin-1 in papillary (TPC-1) and anaplastic (8505C) thyroid cancer cell lines was achieved by lentiviral transduction for in vitro experiments. A murine orthotopic thyroid cancer model was used to investigate tumor growth and metastatic ability. Immunohistochemical analyses of galectin-1 and -3 in the series of 69 cases of thyroid lesions revealed that galectin-1 was completely absent in the epithelial compartment of all benign thyroid lesions. Levels of both galectins significantly increased in the cytoplasmic compartment of malignant thyroid cells. Galectin-1 expression in the TMA yielded an excellent specificity (97%), while galectin-3 and CK19 presented a higher sensitivity (>97%) in discriminating benign from malignant thyroid lesions. In vitro experiments revealed that migration was negatively affected in TPC-1 galectin-1 knockdown (KD) cells, and that proliferation and invasion capacity of 8505C cells decreased after galectin-1 KD. Moreover, an orthotopic mouse model displayed a lower rate of tumor development with galectin-1 KD thyroid anaplastic cancer cells than in the control. Our findings support the introduction of galectin-1 as a reliable diagnostic marker for thyroid carcinomas. Its involvement in cell proliferation, migration, invasion and tumor growth also intimate functional involvement of galectin-1 in the progression of thyroid carcinoma, suggesting its potential as a therapeutic target.

摘要

细针穿刺抽吸术(FNA)是诊断恶性甲状腺肿瘤最常用的术前技术。然而,许多良性病变在 FNA 后诊断不确定,需要手术。基于内源性半乳糖凝集素-1的多功能性,我们旨在评估其在甲状腺癌早期诊断中的地位。对 69 例甲状腺病变的临床系列进行了半乳糖凝集素-1 和 -3 的免疫组织化学染色。在另外两个由 66 例滤泡性腺瘤和 66 例乳头状癌组成的组织微阵列(TMA)中进一步检查了半乳糖凝集素-1 的表达,并与半乳糖凝集素-3 和细胞角蛋白 19(CK19)进行了比较。此外,通过慢病毒转导实现了对甲状腺乳头状(TPC-1)和间变性(8505C)甲状腺癌细胞系中半乳糖凝集素-1 的敲低,用于体外实验。使用鼠原位甲状腺癌模型来研究肿瘤生长和转移能力。对 69 例甲状腺病变系列的半乳糖凝集素-1 和 -3 的免疫组织化学分析表明,半乳糖凝集素-1 完全不存在于所有良性甲状腺病变的上皮细胞区。恶性甲状腺细胞的细胞质区中两种半乳糖凝集素的水平显着增加。TMA 中的半乳糖凝集素-1 表达具有极好的特异性(97%),而半乳糖凝集素-3 和 CK19 在区分良性和恶性甲状腺病变时具有更高的敏感性(>97%)。体外实验表明,在 TPC-1 半乳糖凝集素-1 敲低(KD)细胞中迁移受到负面影响,并且在半乳糖凝集素-1 KD 后 8505C 细胞的增殖和侵袭能力降低。此外,与对照相比,在原位小鼠模型中,半乳糖凝集素-1 KD 甲状腺间变性癌细胞的肿瘤发展速度较低。我们的研究结果支持将半乳糖凝集素-1 作为甲状腺癌的可靠诊断标志物引入。其在细胞增殖、迁移、侵袭和肿瘤生长中的作用也暗示了半乳糖凝集素-1在甲状腺癌进展中的功能参与,表明其作为治疗靶标的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfc/5564411/dc005efe9fa9/IJO-51-03-0760-g00.jpg

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