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