Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas.
Aged
Aged, 80 and over
Brain Neoplasms
/ genetics
Calcitonin Receptor-Like Protein
/ genetics
Cell Culture Techniques
Cell Proliferation
Glioblastoma
/ genetics
Humans
Middle Aged
Mitogen-Activated Protein Kinases
/ metabolism
Phosphorylation
Receptor Activity-Modifying Protein 1
/ genetics
Receptor Activity-Modifying Protein 2
/ genetics
Receptors, Calcitonin
/ genetics
Signal Transduction
Survival Analysis
Transcriptome
p38 Mitogen-Activated Protein Kinases
/ metabolism
Calcitonin receptor
GPCR
Glioblastoma
Signaling
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
18 Feb 2019
18 Feb 2019
Historique:
received:
20
08
2018
accepted:
11
02
2019
entrez:
20
2
2019
pubmed:
20
2
2019
medline:
14
6
2019
Statut:
epublish
Résumé
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 ERK 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.
Sections du résumé
BACKGROUND
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 30777055
doi: 10.1186/s12885-019-5369-y
pii: 10.1186/s12885-019-5369-y
pmc: PMC6379965
doi:
Substances chimiques
CALCRL protein, human
0
Calcitonin Receptor-Like Protein
0
RAMP1 protein, human
0
RAMP2 protein, human
0
Receptor Activity-Modifying Protein 1
0
Receptor Activity-Modifying Protein 2
0
Receptors, Calcitonin
0
Mitogen-Activated Protein Kinases
EC 2.7.11.24
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
157Subventions
Organisme : Natural Science Foundation of Jiangsu Province
ID : BK20160064
Organisme : National Natural Science Foundation of China
ID : 31802222
Organisme : National Key Research and Development Program of China
ID : 2017YFD0500804
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