Simões-Sousa Susana, Granja Sara, Pinheiro Céline, Fernandes Daniela, Longatto-Filho Adhemar, Laus Ana Carolina, Alves Cira Danielle Casado, Suárez-Peñaranda J M, Pérez-Sayáns Mario, Lopes Carvalho Andre, Schmitt Fernando C, García-García Abel, Baltazar Fatima
a Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.
b ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
Cell Cycle. 2016 Jul 17;15(14):1865-73. doi: 10.1080/15384101.2016.1188239. Epub 2016 May 27.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer. The majority of patients present advanced stage disease and has poor survival. Therefore, it is imperative to search for new biomarkers and new alternative and effective treatment options. Most cancer cells rely on aerobic glycolysis to generate energy and metabolic intermediates. This phenotype is a hallmark of cancer, characterized by an increase in glucose consumption and production of high amounts of lactate. Consequently, cancer cells need to up-regulate many proteins and enzymes related with the glycolytic metabolism. Thus, the aim of this study was to characterize metabolic phenotype of oral cavity cancers (OCC) by assessing the expression pattern of monocarboxylate transporters (MCTs) 1, 2 and 4 and other proteins related with the glycolytic phenotype.
We evaluated the immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX in 135 human samples of OCC and investigated the correlation with clinicopathological parameters and the possible association with prognosis.
We observed that all proteins analyzed presented significantly higher plasma membrane expression in neoplastic compared to non-neoplastic samples. MCT4 was significantly associated with T-stage and advanced tumoral stage, while CD147 was significantly correlated with histologic differentiation. Interestingly, tumors expressing both MCT1 and MCT4 but negative for MCT2 were associated with shorter overall survival.
Overexpression of MCT1/4, CD147, GLUT1 and CAIX, supports previous findings of metabolic reprograming in OCC, warranting future studies to explore the hyper-glycolytic phenotype of these tumors. Importantly, MCT expression revealed to have a prognostic value in OCC survival.
头颈部鳞状细胞癌（HNSCC）是第六大常见癌症类型。大多数患者就诊时已处于晚期，生存率低。因此，寻找新的生物标志物以及新的替代且有效的治疗方案势在必行。大多数癌细胞依靠有氧糖酵解来产生能量和代谢中间体。这种表型是癌症的一个标志，其特征是葡萄糖消耗增加以及大量乳酸生成。因此，癌细胞需要上调许多与糖酵解代谢相关的蛋白质和酶。因此，本研究的目的是通过评估单羧酸转运蛋白（MCT）1、2和4以及其他与糖酵解表型相关的蛋白质的表达模式，来表征口腔癌（OCC）的代谢表型。
我们评估了135例人类OCC样本中MCT1、MCT4、CD147、葡萄糖转运蛋白1（GLUT1）和碳酸酐酶IX（CAIX）的免疫组化表达，并研究了其与临床病理参数的相关性以及与预后的可能关联。
我们观察到，与非肿瘤样本相比，所有分析的蛋白质在肿瘤样本中的质膜表达均显著更高。MCT4与T分期和肿瘤晚期显著相关，而CD147与组织学分化显著相关。有趣的是，同时表达MCT1和MCT4但MCT2为阴性的肿瘤与总生存期较短相关。
MCT1/4、CD147、GLUT1和CAIX的过表达支持了先前关于OCC代谢重编程的研究结果，值得未来开展研究以探索这些肿瘤的高糖酵解表型。重要的是，MCT表达显示对OCC生存具有预后价值。
