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TRPM8 protein expression in hormone naïve local and lymph node metastatic prostate cancer
Andrea Lunardi1, Mattia Barbareschi2, Francesco Giuseppe Carbone2
1Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Italy.
Objective:
Prostate cancer (PCa) is the second most common malignancy in men. Radiotherapy and surgery successfully control organ-confined tumors, although, locally advanced/high-risk PCa frequently progress to the metastatic stage of the disease, which is uncurable. Identification of novel strategies to improve the efficacy of standard clinical protocols is a primary need. Among the molecular targets of potential clinical interest recently highlighted by accurate preclinical studies, the TRPM8 cation channel is particularly promising. In this study, we aim at establishing a standardized immunohistochemistry protocol to evaluate TRPM8 expression in normal and pathological prostate tissues.
Methods:
The specificity and sensitivity of TRPM8 antibody ACC-049 was validated in different human prostate cell lines by western blot and immunocytochemistry analyses. Expression of the TRPM8 channel in normal and pathological prostate tissue was evaluated by immunohistochemistry using a tissue microarray containing 58 cases of prostate adenocarcinomas and in primary and lymph nodes metastatic human PCa matched specimens.
Results:
TRPM8 expression marks luminal epithelial cells in benign prostate tissue. In malignant lesions of the prostate, TRPM8 expression is frequently more abundant in advanced stages of the disease (PCa stage III/IV). Finally, lymph node metastases and matched primary tumors show similar amounts of the channel.
Conclusions:
Collectively, our results reinforce the importance of TRPM8 as prostate biomarker and emphasize the value of the channel as promising novel molecular target for the treatment of prostate adenocarcinoma.
Insights
TRPM8 expression is increased in advanced prostate cancer (PCa) and lymph node metastases. This study establishes a protocol to evaluate TRPM8, a promising target for PCa treatment.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Prostate cancer (PCa) is a leading malignancy in men, with advanced stages often becoming metastatic and incurable.
- Current treatments for locally advanced/high-risk PCa require novel strategies to improve efficacy.
- The TRPM8 cation channel is a promising molecular target identified in preclinical studies.
Purpose of the Study:
- To establish a standardized immunohistochemistry protocol for evaluating TRPM8 expression.
- To assess TRPM8 expression in normal and pathological prostate tissues.
- To investigate TRPM8 as a potential biomarker and therapeutic target in prostate cancer.
Main Methods:
- Validated TRPM8 antibody ACC-049 specificity and sensitivity using western blot and immunocytochemistry in prostate cell lines.
- Evaluated TRPM8 expression in normal and pathological prostate tissues via immunohistochemistry.
- Utilized a tissue microarray with 58 prostate adenocarcinomas and matched primary/metastatic specimens.
Main Results:
- TRPM8 expression was observed in luminal epithelial cells of benign prostate tissue.
- TRPM8 levels were frequently higher in advanced PCa stages (III/IV).
- Lymph node metastases and their matched primary tumors exhibited similar TRPM8 expression levels.
Conclusions:
- TRPM8 is confirmed as a significant prostate cancer biomarker.
- TRPM8 holds promise as a novel molecular target for prostate adenocarcinoma treatment.
- The developed protocol enables reliable TRPM8 expression analysis in prostate tissues.
