High P2X6 receptor expression in human bladder cancer predicts good survival prognosis

Dietrich, Fabrícia; Cappellari, Angélica Regina; Filippi-Chiela, Eduardo Cremonese; Paula, Patrícia Boni de; Souza, Julia Brandt de; Agatti, Stefano Walter; Andrejew, Roberta; Roesler, Rafaël; Morrone, Fernanda Bueno; Battastini, Ana Maria Oliveira

doi:10.1007/s11010-022-04425-0

Cited by 4 publications

(5 citation statements)

References 35 publications

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“…P2X1R expression was associated with clinicopathological parameters of tumor progression and shorter median OS and TSS. In agreement, a recent study reported a link between high levels of P2X1R mRNA transcripts and shorter median OS in a cohort of bladder cancer patients from The Cancer Genome Atlas (TCGA) databank [34]. P2X1R expression was also previously implicated in the development of prostate cancer and acute pediatric leukemia [41,42].…”

Section: Discussionsupporting

confidence: 77%

“…Therefore, we first tested in a cell culture model with bladder cells of different grades of malignancy how ATP signaling affects bladder cancer cell proliferation. We used TRT-HU-1 cells, an hTERT-immortalized and non-transformed human urothelial cell line [ 33 ], RT4 cells, a low-grade, well-differentiated, non-invasive papillary transitional cell carcinoma cell line, and T24 cells, a transitional cell carcinoma cell line that was established from a bladder cancer patient with a high-grade, invasive urothelial carcinoma and that expresses various purinergic receptor subtypes [ 34 , 35 ]. ATP accumulation in the TME is driven by hypoxia, cell death, or ATP release from stimulated inflammatory cells [ 8 ].…”

Section: Resultsmentioning

confidence: 99%

“…In addition, other purinergic receptor subtypes might affect malignancy factors such as tumor growth, tumor cell migration, invasion, and metastasis in different types of bladder cancer. Of note, high P2X6R expression was recently associated with prolonged survival in a mixed population of low- and high-grade bladder cancer patients [ 34 ]. Thus, further studies are needed to explore the potential prognostic and therapeutic value of the different P1 and P2 receptor subtypes in MIBC and NMIBC in more detail and define the role of purinergic signaling in bladder cancer development and progression as well as in the antitumor immune response.…”

Section: Discussionmentioning

confidence: 99%

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P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer

Ledderose

Rodler

Eismann

et al. 2023

Cancers

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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.

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Section: Discussionsupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer

Ledderose

Rodler

Eismann

et al. 2023

Cancers

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“…In muscle-invasive bladder cancer, P2X7R has been reported as a negative predictor of overall survival (93). These findings have been validated through TCGA analysis (94). In the setting of renal-cell carcinoma, a study showed that P2X7R expression is an adverse prognostic indicator for postoperative cancer-specific survival (95).…”

Section: Prognostic Value Of P2x7r Expression In Cancermentioning

confidence: 91%

Tumour immune escape via P2X7 receptor signalling

Sainz,

Rodriguez-Quintero,

Maldifassi

et al. 2023

Front. Immunol.

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While P2X7 receptor expression on tumour cells has been characterized as a promotor of cancer growth and metastasis, its expression by the host immune system is central for orchestration of both innate and adaptive immune responses against cancer. The role of P2X7R in anti-tumour immunity is complex and preclinical studies have described opposing roles of the P2X7R in regulating immune responses against tumours. Therefore, few P2X7R modulators have reached clinical testing in cancer patients. Here, we review the prognostic value of P2X7R in cancer, how P2X7R have been targeted to date in tumour models, and we discuss four aspects of how tumours skew immune responses to promote immune escape via the P2X7R; non-pore functional P2X7Rs, mono-ADP-ribosyltransferases, ectonucleotidases, and immunoregulatory cells. Lastly, we discuss alternative approaches to offset tumour immune escape via P2X7R to enhance immunotherapeutic strategies in cancer patients.

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“…Although the two directions of urothelial ATP release are difficult to visualize, its actions on suburothelial tissues, including afferent neurons, ICCs, and detrusor smooth muscle cells, through purinergic signalling pathways are well established. Rodent and human bladder expresses all seven P2X receptors (P2X 1-7 ) and several subtypes of P2Y receptors (P2Y 1 、P2Y 2 、P2Y 4 、P2Y 6 ) [ [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] ].Therefore, the autocrine and paracrine effects of urothelial ATP have been the focus of lower urinary tract research.…”

Section: Functions Of Urothelial Mechanotransductionmentioning

confidence: 99%

Mechanotransduction in the urothelium: ATP signalling and mechanoreceptors

Li,

Hu,

Yin

et al. 2023

Heliyon

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High P2X6 receptor expression in human bladder cancer predicts good survival prognosis

Cited by 4 publications

References 35 publications

P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer

P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer

Tumour immune escape via P2X7 receptor signalling

Mechanotransduction in the urothelium: ATP signalling and mechanoreceptors

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