Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/20302
Title: Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas.
Austin Authors: Ostrovskaya, Anna;Hick, Caroline;Hutchinson, Dana S;Stringer, Brett W;Wookey, Peter J ;Wootten, Denise;Sexton, Patrick M;Furness, Sebastian G B
Affiliation: QIMR-Berghofer Medical Research Institute, Brisbane, QLD, Australia
Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia
School of Pharmacy, Fudan University, Shanghai, 201203, China
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Cardiology, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 18-Feb-2019
metadata.dc.date: 2019-02-18
Publication information: BMC cancer 2019; 19(1): 157
Abstract: 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. 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 ERK1/2 and p38 MAP kinases, and Ca2+ 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. 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20302
DOI: 10.1186/s12885-019-5369-y
ORCID: 0000-0001-8655-8221
0000-0002-3937-1621
PubMed URL: 30777055
Type: Journal Article
Subjects: Calcitonin receptor
GPCR
Glioblastoma
Signaling
Appears in Collections:Journal articles

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