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Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma.
Int J Mol Sci. 2022 Feb 08; 23(3)IJ

Abstract

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.

Authors+Show Affiliations

Somogy County Kaposi Mór Teaching Hospital Kaposvár, H-7400 Kaposvár, Hungary. Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary.1st Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary.1st Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary.Research Group for Mood Disorders, Department of Anatomy & Centre for Neuroscience & Szentágothai Research Centre, University of Pécs Medical School, H-7624 Pécs, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary. Bioinformatics Research Group, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary.Somogy County Kaposi Mór Teaching Hospital Kaposvár, H-7400 Kaposvár, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary. Department of Pharmacology, Faculty of Pharmacy, University of Pécs, H-7624 Pécs, Hungary.Department of Pharmacology and Pharmacotherapy, University of Pécs Medical School, H-7624 Pécs, Hungary. Centre for Neuroscience, University of Pécs János Szentágothai Research Centre, H-7624 Pécs, Hungary. PharmInVivo Ltd., H-7629 Pécs, Hungary.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35163843

Citation

Kiss, Fruzsina, et al. "Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma." International Journal of Molecular Sciences, vol. 23, no. 3, 2022.
Kiss F, Kormos V, Szőke É, et al. 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(3).
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. (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(3). https://doi.org/10.3390/ijms23031921
Kiss F, et al. Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma. Int J Mol Sci. 2022 Feb 8;23(3) PubMed PMID: 35163843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional Transient Receptor Potential Ankyrin 1 and Vanilloid 1 Ion Channels Are Overexpressed in Human Oral Squamous Cell Carcinoma. AU - Kiss,Fruzsina, AU - Kormos,Viktória, AU - Szőke,Éva, AU - Kecskés,Angéla, AU - Tóth,Norbert, AU - Steib,Anita, AU - Szállási,Árpád, AU - Scheich,Bálint, AU - Gaszner,Balázs, AU - Kun,József, AU - Fülöp,Gábor, AU - Pohóczky,Krisztina, AU - Helyes,Zsuzsanna, Y1 - 2022/02/08/ PY - 2021/12/15/received PY - 2022/02/03/revised PY - 2022/02/06/accepted PY - 2022/2/15/entrez PY - 2022/2/16/pubmed PY - 2022/3/8/medline KW - AITC KW - ATP-based luminescence KW - RNAscope KW - TRPA1 KW - TRPV1 KW - capsaicin KW - cell viability KW - diagnostic and prognostic biomarker KW - oral squamous cell carcinoma KW - radioactive 45Ca2+ uptake JF - International journal of molecular sciences JO - Int J Mol Sci VL - 23 IS - 3 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/35163843/Functional_Transient_Receptor_Potential_Ankyrin_1_and_Vanilloid_1_Ion_Channels_Are_Overexpressed_in_Human_Oral_Squamous_Cell_Carcinoma_ L2 - https://www.mdpi.com/resolver?pii=ijms23031921 DB - PRIME DP - Unbound Medicine ER -