Inflammation is a common condition of prostate tissue, whose impact on carcinogenesis is highly debated. Microbial colonization is a well-documented cause of a small percentage of prostatitis cases, but it remains unclear what underlies the majority of sterile inflammation reported. Here, androgen- independent fluctuations of PSA expression in prostate cells have lead us to identify a prominent function of the Transient Receptor Potential Cation Channel Subfamily M Member 8 (TRPM8) gene in sterile inflammation. Prostate cells secret TRPM8 RNA into extracellular vesicles (EVs), which primes TLR3/NF-kB-mediated inflammatory signaling after EV endocytosis by epithelial cancer cells. Furthermore, prostate cancer xenografts expressing a translation-defective form of TRPM8 RNA contain less collagen type I in the extracellular matrix, significantly more infiltrating NK cells, and larger necrotic areas as compared to control xenografts. These findings imply sustained, androgen-independent expression of TRPM8 constitutes as a promoter of anticancer innate immunity, which may constitute a clinically relevant condition affecting prostate cancer prognosis.
The EMBO journal. 2024 Feb 05 [Epub ahead of print]
Alessandro Alaimo, Sacha Genovesi, Nicole Annesi, Dario De Felice, Saurav Subedi, Alice Macchia, Federico La Manna, Yari Ciani, Federico Vannuccini, Vera Mugoni, Michela Notarangelo, Michela Libergoli, Francesca Broso, Riccardo Taulli, Ugo Ala, Aurora Savino, Martina Cortese, Somayeh Mirzaaghaei, Valeria Poli, Ian Marc Bonapace, Mauro Giulio Papotti, Luca Molinaro, Claudio Doglioni, Orazio Caffo, Adriano Anesi, Michael Nagler, Giovanni Bertalot, Francesco Giuseppe Carbone, Mattia Barbareschi, Umberto Basso, Erik Dassi, Massimo Pizzato, Alessandro Romanel, Francesca Demichelis, Marianna Kruithof-de Julio, Andrea Lunardi
Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy. ., Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Department for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland., Department of Oncology, University of Torino, Torino, Italy., Department of Veterinary Sciences, University of Torino, Torino, Italy., Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy., Department of Biotechnology and Life Sciences, University of Insubria, Busto Arsizio, VA, Italy., Department of Pathology, University of Torino and AOU Città della Salute e della Scienza di Torino, Torino, Italy., Division of Pathology, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS Vita Salute, San Raffaele University, Milano, Italy., Medical Oncology Department, Santa Chiara Hospital-APSS, Trento, Italy., Operative Unit of Clinical Pathology, Santa Chiara Hospital-APSS, Trento, Italy., Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Operative Unit of Anatomy Pathology, Santa Chiara Hospital-APSS, Trento, Italy., Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy., Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy. .