Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas

Anna Ostrovskaya, Caroline Hick, Dana S. Hutchinson, Brett W. Stringer, Peter J. Wookey, Denise Wootten, Patrick M. Sexton, Sebastian G.B. Furness

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Glioblastoma (GBM) is the most common and aggressive type of primary brain cancer. With median survival of less than 15 months, identification and validation of new GBM therapeutic targets is of critical importance. Results: In this study we tested expression and performed pharmacological characterization of the calcitonin receptor (CTR) as well as other members of the calcitonin family of receptors in high-grade glioma (HGG) cell lines derived from individual patient tumours, cultured in defined conditions. Previous immunohistochemical data demonstrated CTR expression in GBM biopsies and we were able to confirm CALCR (gene encoding CTR) expression. However, as assessed by cAMP accumulation assay, only one of the studied cell lines expressed functional CTR, while the other cell lines have functional CGRP (CLR/RAMP1) receptors. The only CTR-expressing cell line (SB2b) showed modest coupling to the cAMP pathway and no activation of other known CTR signaling pathways, including ERK 1/2 and p38 MAP kinases, and Ca 2+ mobilization, supportive of low cell surface receptor expression. Exome sequencing data failed to account for the discrepancy between functional data and expression on the cell lines that do not respond to calcitonin(s) with no deleterious non-synonymous polymorphisms detected, suggesting that other factors may be at play, such as alternative splicing or rapid constitutive receptor internalisation. Conclusions: This study shows that GPCR signaling can display significant variation depending on cellular system used, and effects seen in model recombinant cell lines or tumour cell lines are not always reproduced in a more physiologically relevant system and vice versa.

Original languageEnglish
Article number157
Number of pages12
JournalBMC Cancer
Volume19
DOIs
Publication statusPublished - 18 Feb 2019
Externally publishedYes

Bibliographical note

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Keywords

  • Calcitonin receptor
  • Glioblastoma
  • GPCR
  • Signaling

Fingerprint Dive into the research topics of 'Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas'. Together they form a unique fingerprint.

  • Cite this

    Ostrovskaya, A., Hick, C., Hutchinson, D. S., Stringer, B. W., Wookey, P. J., Wootten, D., Sexton, P. M., & Furness, S. G. B. (2019). Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas. BMC Cancer, 19, [157]. https://doi.org/10.1186/s12885-019-5369-y