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

Sophie Orton, Rebecca Karkia, Denis Mustafov, Seley Gharanei, Maria Braoudaki, Alice Filipe, Suzana Panfilov, Sayeh Saravi, Nabeel Khan, Ioannis Kyrou, Emmanouil Karteris, Jayanta Chatterjee, Harpal S. Randeva

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Abstract

Simple Summary: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) plays a role in cell proliferation, differentiation, oncogenic transformation, and brain development and serves as an orexigenic asprosin receptor. This study investigates the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). 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 by obesity. Using a tissue microarray, abundant PTPRD expression in low- and high-grade EC tumours is noted. Using liquid biopsies from EC patients, we show the expression of PTPRD in peripheral leukocytes. Moreover, asprosin treatment upregulates the expression of PTPRD in syncytialised placental cells in vitro, but not in EC cell lines. Collectively, our data suggest 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. Abstract: 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.
Original languageEnglish
Article number582
Number of pages219
JournalCancers
Volume16
Issue number3
Early online date30 Jan 2024
DOIs
Publication statusE-pub ahead of print - 30 Jan 2024

Bibliographical note

© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Funder

This research was funded by GRACE, Registered Charity No. 1189729 and by the General Charities of the City of Coventry, Registered Charity No. 216235.

Keywords

  • PTPRD
  • glioblastoma
  • protein tyrosine phosphatase receptor type D
  • asprosin
  • endometrial cancer
  • placenta

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