P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer
Bladder cancer is amongst the most common causes of cancer death worldwide. Muscle-invasive bladder cancer (MIBC) bears a particularly poor prognosis. Overexpression of purinergic P2X receptors (P2XRs) has been associated with worse outcome in several malignant tumors. Here, we investigated the role...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/8/2321 |
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| author | Stephan Ledderose Severin Rodler Lennert Eismann Georg Ledderose Martina Rudelius Wolfgang G. Junger Carola Ledderose |
| author_facet | Stephan Ledderose Severin Rodler Lennert Eismann Georg Ledderose Martina Rudelius Wolfgang G. Junger Carola Ledderose |
| author_sort | Stephan Ledderose |
| collection | DOAJ |
| description | Bladder cancer is amongst the most common causes of cancer death worldwide. Muscle-invasive bladder cancer (MIBC) bears a particularly poor prognosis. Overexpression of purinergic P2X receptors (P2XRs) has been associated with worse outcome in several malignant tumors. Here, we investigated the role of P2XRs in bladder cancer cell proliferation in vitro and the prognostic value of P2XR expression in MIBC patients. Cell culture experiments with T24, RT4, and non-transformed TRT-HU-1 cells revealed a link between high ATP concentrations in the cell culture supernatants of bladder cell lines and a higher grade of malignancy. Furthermore, proliferation of highly malignant T24 bladder cancer cells depended on autocrine signaling through P2X receptors. P2X1R, P2X4R, and P2X7R expression was immunohistochemically analyzed in tumor specimens from 173 patients with MIBC. High P2X1R expression was associated with pathological parameters of disease progression and reduced survival time. High combined expression of P2X1R and P2X7R increased the risk of distant metastasis and was an independent negative predictor of overall and tumor-specific survival in multivariate analyses. Our results suggest that P2X1R/P2X7R expression scores are powerful negative prognostic markers in MIBC patients and that P2XR-mediated pathways are potential targets for novel therapeutic strategies in bladder cancer. |
| first_indexed | 2024-03-11T05:10:16Z |
| format | Article |
| id | doaj.art-976cc5fabd5245e8a3923011b92bb8f0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:10:16Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-976cc5fabd5245e8a3923011b92bb8f02023-11-17T18:39:22ZengMDPI AGCancers2072-66942023-04-01158232110.3390/cancers15082321P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder CancerStephan Ledderose0Severin Rodler1Lennert Eismann2Georg Ledderose3Martina Rudelius4Wolfgang G. Junger5Carola Ledderose6Institute of Pathology, Ludwig Maximilian University, 80337 Munich, GermanyDepartment of Urology, Ludwig Maximilian University, 81377 Munich, GermanyDepartment of Urology, Ludwig Maximilian University, 81377 Munich, GermanyDepartment of Oto-Rhino-Laryngology, Ludwig Maximilian University, 81377 Munich, GermanyInstitute of Pathology, Ludwig Maximilian University, 80337 Munich, GermanyDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USABladder cancer is amongst the most common causes of cancer death worldwide. Muscle-invasive bladder cancer (MIBC) bears a particularly poor prognosis. Overexpression of purinergic P2X receptors (P2XRs) has been associated with worse outcome in several malignant tumors. Here, we investigated the role of P2XRs in bladder cancer cell proliferation in vitro and the prognostic value of P2XR expression in MIBC patients. Cell culture experiments with T24, RT4, and non-transformed TRT-HU-1 cells revealed a link between high ATP concentrations in the cell culture supernatants of bladder cell lines and a higher grade of malignancy. Furthermore, proliferation of highly malignant T24 bladder cancer cells depended on autocrine signaling through P2X receptors. P2X1R, P2X4R, and P2X7R expression was immunohistochemically analyzed in tumor specimens from 173 patients with MIBC. High P2X1R expression was associated with pathological parameters of disease progression and reduced survival time. High combined expression of P2X1R and P2X7R increased the risk of distant metastasis and was an independent negative predictor of overall and tumor-specific survival in multivariate analyses. Our results suggest that P2X1R/P2X7R expression scores are powerful negative prognostic markers in MIBC patients and that P2XR-mediated pathways are potential targets for novel therapeutic strategies in bladder cancer.https://www.mdpi.com/2072-6694/15/8/2321bladder cancermuscle-invasive bladder cancerATPpurinergic signalingP2X receptorsP2X1 receptor |
| spellingShingle | Stephan Ledderose Severin Rodler Lennert Eismann Georg Ledderose Martina Rudelius Wolfgang G. Junger Carola Ledderose P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer Cancers bladder cancer muscle-invasive bladder cancer ATP purinergic signaling P2X receptors P2X1 receptor |
| title | P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer |
| title_full | P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer |
| title_fullStr | P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer |
| title_full_unstemmed | P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer |
| title_short | P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer |
| title_sort | p2x1 and p2x7 receptor overexpression is a negative predictor of survival in muscle invasive bladder cancer |
| topic | bladder cancer muscle-invasive bladder cancer ATP purinergic signaling P2X receptors P2X1 receptor |
| url | https://www.mdpi.com/2072-6694/15/8/2321 |
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