Sobrinho Santos Eliane Macedo, Guimarães Talita Antunes, Santos Hércules Otacílio, Cangussu Lilian Mendes Borborema, de Jesus Sabrina Ferreira, Fraga Carlos Alberto de Carvalho, Cardoso Claudio Marcelo, Santos Sérgio Henrique Souza, de Paula Alfredo Maurício Batista, Gomez Ricardo Santiago, Guimarães André Luiz Sena, Farias Lucyana Conceição
1 Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Brazil.
2 Instituto Federal do Norte de Minas Gerais-Campus Araçuaí, Montes Claros, Brazil.
Tumour Biol. 2017 May;39(5):1010428317699130. doi: 10.1177/1010428317699130.
Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.
瘦素是控制能量平衡的主要激素之一，已被发现与多种癌症类型相关。在口腔癌中，其作用尚不清楚。我们通过体外和体内试验，研究了瘦素是否会影响口腔鳞状细胞癌的肿瘤行为。在经瘦素处理的口腔鳞状细胞癌细胞以及口腔鳞状细胞癌和口腔黏膜的组织样本中，评估了可能与瘦素信号通路相关的基因表达，包括瘦素、瘦素受体、缺氧诱导因子1-α、E-钙黏蛋白、基质金属蛋白酶-2、基质金属蛋白酶-9、I型胶原α1链（Col1A1）、Ki67和mir-210。瘦素处理促进了更高的细胞增殖率和迁移率，并减少了细胞凋亡。相应地，经瘦素处理的口腔鳞状细胞癌细胞显示半胱天冬酶-3信使核糖核酸表达降低，而E-钙黏蛋白、Col1A1、基质金属蛋白酶-2、基质金属蛋白酶-9和mir-210水平升高。在组织样本中，口腔鳞状细胞癌病例中缺氧诱导因子1-α信使核糖核酸以及瘦素和瘦素受体的蛋白表达较高。在疾病的首个临床阶段，血清瘦素水平升高。在动物模型中，口腔鳞状细胞癌诱导的小鼠显示出更高的瘦素受体表达，发育异常组的血清瘦素水平升高。我们的研究结果表明，瘦素似乎对口腔鳞状细胞癌细胞行为以及与细胞增殖、迁移和肿瘤血管生成相关的分子标志物都有影响。
