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Article

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

1
Somogy County Kaposi Mór Teaching Hospital Kaposvár, H-7400 Kaposvár, Hungary
2
Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary
3
Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary
4
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary
5
Research Group for Mood Disorders, Department of Anatomy & Centre for Neuroscience & Szentágothai Research Centre, University of Pécs Medical School, H-7624 Pécs, Hungary
6
Bioinformatics Research Group, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary
7
Department of Pharmacology, Faculty of Pharmacy, University of Pécs, H-7624 Pécs, Hungary
8
PharmInVivo Ltd., H-7629 Pécs, Hungary
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Athanasios G. Papavassiliou
Int. J. Mol. Sci. 2022, 23(3), 1921; https://doi.org/10.3390/ijms23031921
Received: 15 December 2021 / Revised: 3 February 2022 / Accepted: 6 February 2022 / Published: 8 February 2022
(This article belongs to the Section Molecular Biology)
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. TRPA1 and TRPV1 mRNA were determined by RNAscope in situ hybridization and qPCR. Radioactive 45Ca2+ 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 TRPA1 and TRPV1 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 45Ca2+-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. View Full-Text
Keywords: RNAscope; radioactive 45Ca2+ uptake; cell viability; ATP-based luminescence; oral squamous cell carcinoma; diagnostic and prognostic biomarker; AITC; capsaicin; TRPA1; TRPV1 RNAscope; radioactive 45Ca2+ uptake; cell viability; ATP-based luminescence; oral squamous cell carcinoma; diagnostic and prognostic biomarker; AITC; capsaicin; TRPA1; TRPV1
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MDPI and ACS Style

Kiss, F.; Kormos, V.; Szőke, É.; Kecskés, A.; Tóth, N.; Steib, A.; Szállási, Á.; Scheich, B.; Gaszner, B.; Kun, J.; Fülöp, G.; Pohóczky, K.; Helyes, Z. Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma. Int. J. Mol. Sci. 2022, 23, 1921. https://doi.org/10.3390/ijms23031921

AMA Style

Kiss F, Kormos V, Szőke É, Kecskés A, Tóth N, Steib A, Szállási Á, Scheich B, Gaszner B, Kun J, Fülöp G, Pohóczky K, Helyes Z. Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2022; 23(3):1921. https://doi.org/10.3390/ijms23031921

Chicago/Turabian Style

Kiss, Fruzsina, Viktória Kormos, Éva Szőke, Angéla Kecskés, Norbert Tóth, Anita Steib, Árpád Szállási, Bálint Scheich, Balázs Gaszner, József Kun, Gábor Fülöp, Krisztina Pohóczky, and Zsuzsanna Helyes. 2022. "Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma" International Journal of Molecular Sciences 23, no. 3: 1921. https://doi.org/10.3390/ijms23031921

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