Orton Sophie, Karkia Rebecca, Mustafov Denis, Gharanei Seley, Braoudaki Maria, Filipe Alice, Panfilov Suzana, Saravi Sayeh, Khan Nabeel, Kyrou Ioannis, Karteris Emmanouil, Chatterjee Jayanta, Randeva Harpal S
Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge UB8 3PH, UK.
Cancers (Basel). 2024 Jan 30;16(3):582. doi: 10.3390/cancers16030582.
Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM).
An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM.
PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells.
Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.
蛋白酪氨酸磷酸酶受体D型（PTPRD）参与细胞生长、分化和致癌转化的调控，以及大脑发育过程。PTPRD还介导了脂肪生成素的作用，脂肪生成素是一种在原纤蛋白1的C末端裂解后产生的生糖激素/脂肪因子。由于在某些癌症中循环中的脂肪生成素水平升高，目前的研究集中在这种脂肪因子及其受体在癌症中的潜在作用。因此，在本研究中，我们调查了PTPRD在子宫内膜癌（EC）、胎盘以及胶质母细胞瘤（GBM）中的表达情况。
使用一系列电子工具、体外模型、组织微阵列（TMA）和液体活检来确定PTPRD在健康组织/器官以及EC和GBM患者中的基因和蛋白表达。
PTPRD在枕叶、顶叶、苍白球、腹侧丘脑和白质中高表达，而在人胎盘中，它主要定位于三级绒毛周围。与健康对照相比，EC和GBM患者的PTPRD在mRNA和蛋白水平上显著上调。在EC患者中，PTPRD随着肥胖而显著下调，同时它也在外周血白细胞中表达。EC组织微阵列显示，在低级别和高级别肿瘤中PTPRD均有丰富表达。脂肪生成素处理仅上调了合体化胎盘细胞中PTPRD的表达。
我们的数据表明，PTPRD可能作为EC和GBM等恶性肿瘤的生物标志物具有潜力，进一步表明脂肪生成素是这些癌症中潜在的代谢调节因子。未来需要开展研究，以探索在癌症中连接PTPRD和脂肪生成素的潜在分子机制/信号通路。
