Madunić Ivana Vrhovac, Madunić Josip, Breljak Davorka, Karaica Dean, Sabolić Ivan
Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Division of Molecular Biology, Department of Molecular Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
Arh Hig Rada Toksikol. 2018 Dec 1;69(4):278-285. doi: 10.2478/aiht-2018-69-3204.
Glucose, the key source of metabolic energy, is imported into cells by two categories of transporters: 1) facilitative glucose transporters (GLUTs) and 2) secondary active sodium-glucose cotransporters (SGLTs). Cancer cells have an increased demand for glucose uptake and utilisation compared to normal cells. Previous studies have demonstrated the overexpression of GLUTs, mainly GLUT1, in many cancer types. As the current standard positron emission tomography (PET) tracer 2-deoxy-2-(18F)fluoro-D-glucose (2-FDG) for imaging tumour cells via GLUT1 lacks in sensitivity and specificity, it may soon be replaced by the newly designed, highly sensitive and specific SGLT tracer α-methyl-4-(F-18)fluoro-4-deoxy-Dglucopyranoside (Me-4FDG) in clinical detection and tumour staging. This tracer has recently demonstrated the functional activity of SGLT in pancreatic, prostate, and brain cancers. The mRNA and protein expression of SGLTs have also been reported in colon/colorectal, lung, ovarian, head, neck, and oral squamous carcinomas. So far, SGLTs have been poorly investigated in cancer, and their protein expression and localisation are often controversial due to a lack of specific SGLT antibodies. In this review, we describe current knowledge concerning SGLT1 and SGLT2 (over)expression in various cancer types. The findings of SGLTs in malignant cells may help in developing novel cancer therapies with SGLT2 or SGLT1/SGLT2 inhibitors already used in diabetes mellitus treatment.
葡萄糖作为代谢能量的关键来源，通过两类转运蛋白进入细胞：1）易化葡萄糖转运蛋白（GLUTs）和2）继发性主动钠-葡萄糖协同转运蛋白（SGLTs）。与正常细胞相比，癌细胞对葡萄糖摄取和利用的需求增加。先前的研究表明，在许多癌症类型中，GLUTs主要是GLUT1存在过表达。由于目前用于通过GLUT1对肿瘤细胞进行成像的标准正电子发射断层扫描（PET）示踪剂2-脱氧-2-（18F）氟-D-葡萄糖（2-FDG）缺乏敏感性和特异性，它可能很快会被新设计的、高度敏感和特异的SGLT示踪剂α-甲基-4-（F-18）氟-4-脱氧-D-吡喃葡萄糖苷（Me-4FDG）取代，用于临床检测和肿瘤分期。这种示踪剂最近已在胰腺癌、前列腺癌和脑癌中证实了SGLT的功能活性。在结肠癌/直肠癌、肺癌、卵巢癌、头颈癌和口腔鳞状细胞癌中也报道了SGLTs的mRNA和蛋白表达。到目前为止，SGLTs在癌症中的研究较少，由于缺乏特异性SGLT抗体，它们的蛋白表达和定位往往存在争议。在这篇综述中，我们描述了目前关于SGLT1和SGLT2在各种癌症类型中（过）表达的知识。SGLTs在恶性细胞中的研究结果可能有助于利用已用于糖尿病治疗的SGLT2或SGLT1/SGLT2抑制剂开发新的癌症治疗方法。
