We have located links that may give you full text access.
P2Y2R-mediated inflammasome activation is involved in tumor progression in breast cancer cells and in radiotherapy-resistant breast cancer.
International Journal of Oncology 2018 November
In the tumor microenvironment, extracellular nucleotides are released and accumulate, and can activate the P2Y2 receptor (P2Y2R), which regulates various responses in tumor cells, resulting in tumor progression and metastasis. Moreover, the inflammasome has recently been reported to be associated with tumor progression. However, the role of P2Y2R in inflammasome activation in breast cancer cells is not yet well defined. Therefore, in this study, we investigated the role of P2Y2R in inflammasome-mediated tumor progression in breast cancer using breast cancer cells and radiotherapy-resistant (RT‑R) breast cancer cells. We established RT‑R-breast cancer cells (RT‑R‑MDA‑MB‑231, RT‑R‑MCF‑7, and RT‑R-T47D cells) by repeated irradiation (2 Gy each, 25 times) in a previous study. In this study, we found that the RT‑R breast cancer cells exhibited an increased release of adenosine triphosphate (ATP) and P2Y2R activity. In particular, the RT‑R‑MDA‑MB‑231 cells derived from highly metastatic MDA‑MB‑231 cells, exhibited a markedly increased ATP release, which was potentiated by tumor necrosis factor (TNF)-α. The MDA‑MB‑231 cells exhibited inflammasome activation, as measured by caspase‑1 activity and interleukin (IL)-1β secretion following treatment with TNF‑α and ATP; these effects were enhanced in the RT‑R‑MDA‑MB‑231 cells. However, the increased caspase‑1 activities and IL‑1β secretion levels induced in response to treatment with TNF‑α or ATP were significantly reduced by P2Y2R knockdown or the presence of apyrase in both the MDA‑MB‑231 and RT‑R‑MDA‑MB‑231 cells, suggesting the involvement of ATP-activated P2Y2R in inflammasome activation. In addition, TNF‑α and ATP increased the invasive and colony-forming ability of the MDA‑MB‑231 and RT‑R‑MDA‑MB‑231 cells, and these effects were caspase‑1-dependent. Moreover, matrix metalloproteinase (MMP)-9 activity was modulated by caspase-1, in a P2Y2R-dependent manner in the MDA‑MB‑231 and RT‑R‑MDA‑MB‑231 cells. Finally, nude mice injected with the RT‑R‑MDA‑MB‑231-EV cells (transfected with the empty vector) exhibited increased tumor growth, and higher levels of MMP-9 in their tumors and IL‑1β levels in their serum compared with the mice injected with the RT‑R‑MDA‑MB‑231-P2Y2R shRNA cells (transfected with P2Y2R shRNA). On the whole, the findings of this study suggest that extracellular ATP promotes tumor progression in RT‑R-breast cancer cells and breast cancer cells by modulating invasion and associated molecules through the P2Y2R-inflammasome activation pathway.
Full text links
Trending Papers
A Personalized Approach to the Management of Congestion in Acute Heart Failure.Heart International 2023
Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium-Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure.International Journal of Molecular Sciences 2024 Februrary 21
The Effect of Albumin Administration in Critically Ill Patients: A Retrospective Single-Center Analysis.Critical Care Medicine 2024 Februrary 8
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app