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文章:

受体型蛋白酪氨酸磷酸酶D在健康与疾病中的计算机模拟与体外定位:对子宫内膜癌和神经母细胞瘤中白脂素信号传导的启示

In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma

原文发布日期:30 January 2024

DOI: 10.3390/cancers16030582

类型: Article

开放获取: 是

 

英文摘要:

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

 

摘要翻译: 

背景:D型蛋白酪氨酸磷酸酶受体(PTPRD)参与细胞生长、分化和致癌转化的调控,并在大脑发育中发挥作用。PTPRD还介导白脂素的作用,白脂素是一种源自原纤维蛋白1 C端裂解的糖原生成激素/脂肪因子。由于白脂素循环水平在某些癌症中升高,目前研究聚焦于该脂肪因子及其受体在癌症中的潜在作用。因此,本研究探讨了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。 方法:采用多种生物信息学工具、体外模型、组织微阵列(TMAs)和液体活检技术,检测PTPRD在健康组织/器官以及EC和GBM患者中的基因和蛋白表达水平。 结果:PTPRD在枕叶、顶叶、苍白球、腹侧丘脑和白质中高表达,而在人类胎盘中主要定位于三级绒毛周围。与健康对照组相比,EC和GBM患者中PTPRD在mRNA和蛋白水平均显著上调。在EC患者中,PTPRD表达随肥胖显著下调,同时在外周白细胞中也有表达。EC组织微阵列显示PTPRD在低级别和高级别肿瘤中均有丰富表达。白脂素处理仅能上调合体化胎盘细胞中PTPRD的表达。 结论:我们的数据表明PTPRD可能作为EC和GBM等恶性肿瘤的潜在生物标志物,进一步提示白脂素在这些癌症中可能作为代谢调节因子。未来研究需深入探索PTPRD与白脂素在癌症中相互关联的潜在分子机制/信号通路。

 

原文链接:

In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma

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