Tools
Tools
Tattersall, Luke, Shah, Karan, Lath, Darren, Singh, Archana, Down, Jennifer, de Marchi, Elena, Williamson, Alex, di Virgilio, Francesco, Heymann, Dominique, Adinolfi, Elena, Fraser, William, Green, Darrell 
ORCID: https://orcid.org/0000-0002-0217-3322, Lawson, Michelle and Gartland, Alison
(2021)
The P2RX7B splice variant modulates osteosarcoma cell behaviour and metastatic properties.
Journal of Bone Oncology, 31.
ISSN 2212-1374
Preview |
PDF (Published_Version)
- Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (3MB) | Preview |
Abstract
Background: Osteosarcoma (OS) is the most common type of primary bone cancer affecting children and adolescents. OS has a high propensity to spread meaning the disease is often incurable and fatal. There have been no improvements in survival rates for decades. This highlights an urgent need for the development of novel therapeutic strategies. Here, we report in vitro and in vivo data that demonstrates the role of purinergic signalling, specifically, the B isoform of the purinergic receptor P2RX7 (P2RX7B), in OS progression and metastasis. Methods: TE85 and MNNG-HOS OS cells were transfected with P2RX7B. These cell lines were then characterised and assessed for proliferation, cell adhesion, migration and invasion in vitro. We used these cells to perform both paratibial and tail vein injected mouse studies where the primary tumour, bone and lungs were analysed. We used RNA-seq to identify responsive pathways relating to P2RX7B. Results: Our data shows that P2RX7B expression confers a survival advantage in TE85 + P2RX7B and MNNG-HOS + P2RX7B human OS cell lines in vitro that is minimised following treatment with A740003, a specific P2RX7 antagonist. P2RX7B expression reduced cell adhesion and P2RX7B activation promoted invasion and migration in vitro, demonstrating a metastatic phenotype. Using an in vivo OS xenograft model, MNNG-HOS + P2RX7B tumours exhibited cancer-associated ectopic bone formation that was abrogated with A740003 treatment. A pro-metastatic phenotype was further demonstrated in vivo as expression of P2RX7B in primary tumour cells increased the propensity of tumour cells to metastasise to the lungs. RNA-seq identified a novel gene axis, FN1/LOX/PDGFB/IGFBP3/BMP4, downregulated in response to A740003 treatment. Conclusion: Our data illustrates a role for P2RX7B in OS tumour growth, progression and metastasis. We show that P2RX7B is a future therapeutic target in human OS.
| Item Type: | Article |
|---|---|
| Additional Information: | Acknowledgements: We would like to thank the Bone Cancer Research Trust for funding this work (Grant number 4415 awarded to A.G), and the Bone Analysis Laboratory within the Department of Oncology and Metabolism for technical assistance. |
| Uncontrolled Keywords: | atp,bone cancer,osteosarcoma,p2rx7b,purinergic signalling,oncology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 21 Oct 2021 01:26 |
| Last Modified: | 19 Oct 2023 03:07 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/81850 |
| DOI: | 10.1016/j.jbo.2021.100398 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |