Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1921
• Main Authors: Kiss, Fruzsina, Kormos, Viktória, Szőke, Éva, Kecskés, Angéla, Tóth, Norbert, Steib, Anita, Szállási, Árpád, Scheich, Bálint, Gaszner, Balázs, Kun, József, Fülöp, Gábor, Pohóczky, Krisztina, Helyes, Zsuzsanna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.02.2022; MDPI
• Subjects: Aged; Aged, 80 and over; Agonists; ATP-based luminescence; Calcium - metabolism; Capsaicin; Capsaicin - pharmacology; Capsaicin receptors; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; diagnostic and prognostic biomarker; Epithelium; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Hybridization; Immune system; Immunoreactivity; In Situ Hybridization; Ion channels; Isothiocyanate; Isothiocyanates - pharmacology; Male; Medical prognosis; Middle Aged; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; mRNA; Mucosa; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Prostate cancer; radioactive 45Ca2+ uptake; RNAscope; Selectivity; Sensory neurons; Squamous cell carcinoma; Tongue; Transient receptor potential proteins; TRPA1 Cation Channel - genetics; TRPA1 Cation Channel - metabolism; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Up-Regulation - drug effects; radioactive 45Ca2+ uptake; cell viability; ATP-based luminescence; TRPA1; capsaicin; diagnostic and prognostic biomarker; AITC; oral squamous cell carcinoma; RNAscope; TRPV1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031921

Oral squamous cell carcinoma (OSCC) is a common cancer with poor prognosis. Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) receptors are non-selective cation channels expressed on primary sensory neurons and epithelial and immune cells. TRPV1 mRNA and immunopositivity, as well as TRPA1-like immunoreactivity upregulation, were demonstrated in OSCC, but selectivity problems with the antibodies still raise questions and their functional relevance is unclear. Therefore, here, we investigated TRPA1 and TRPV1 expressions in OSCC and analyzed their functions. and mRNA were determined by RNAscope in situ hybridization and qPCR. Radioactive Ca uptake and ATP-based luminescence indicating cell viability were measured in PE/CA-PJ41 cells in response to the TRPA1 agonist allyl-isothiocyanate (AITC) and TRPV1 agonist capsaicin to determine receptor function. Both and mRNA are expressed in the squamous epithelium of the human oral mucosa and in PE/CA-PJ41 cells, and their expressions are significantly upregulated in OSCC compared to healthy mucosa. TRPA1 and TRPV1 activation (100 µM AITC, 100 nM capsaicin) induced Ca -influx into PE/CA-PJ41 cells. Both AITC (10 nM-5 µM) and capsaicin (100 nM-45 µM) reduced cell viability, reaching significant decrease at 100 nM AITC and 45 µM capsaicin. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the OSCC and confirm the expression of TRPV1 channel. These channels are functionally active and might regulate cancer cell viability.