Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment
Abstract Oral cancer patients report sensitivity to spicy foods and liquids. The mechanism responsible for chemosensitivity induced by oral cancer is not known. We simulate oral cancer-induced chemosensitivity in a xenograft oral cancer mouse model using two-bottle choice drinking and conditioned pl...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-08005-6 |
| _version_ | 1819294573633994752 |
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| author | Nicole N. Scheff Ian M. Wall Sam Nicholson Hannah Williams Elyssa Chen Nguyen H. Tu John C. Dolan Cheng Z. Liu Malvin N. Janal Nigel W. Bunnett Brian L. Schmidt |
| author_facet | Nicole N. Scheff Ian M. Wall Sam Nicholson Hannah Williams Elyssa Chen Nguyen H. Tu John C. Dolan Cheng Z. Liu Malvin N. Janal Nigel W. Bunnett Brian L. Schmidt |
| author_sort | Nicole N. Scheff |
| collection | DOAJ |
| description | Abstract Oral cancer patients report sensitivity to spicy foods and liquids. The mechanism responsible for chemosensitivity induced by oral cancer is not known. We simulate oral cancer-induced chemosensitivity in a xenograft oral cancer mouse model using two-bottle choice drinking and conditioned place aversion assays. An anatomic basis of chemosensitivity is shown in increased expression of TRPV1 in anatomically relevant trigeminal ganglion (TG) neurons in both the xenograft and a carcinogen (4-nitroquinoline 1-oxide)-induced oral cancer mouse models. The percent of retrograde labeled TG neurons that respond to TRPV1 agonist, capsaicin, is increased along with the magnitude of response as measured by calcium influx, in neurons from the cancer models. To address the possible mechanism of TRPV1 sensitivity in tongue afferents, we study the role of PAR2, which can sensitize the TRPV1 channel. We show co-expression of TRPV1 and PAR2 on tongue afferents and using a conditioned place aversion assay, demonstrate that PAR2 mediates oral cancer-induced, TRPV1-evoked sensitivity in an oral cancer mouse model. The findings provide insight into oral cancer-mediated chemosensitivity. |
| first_indexed | 2024-12-24T04:28:28Z |
| format | Article |
| id | doaj.art-18f2ffcae6f84a02abb412b9786e83d1 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-24T04:28:28Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-18f2ffcae6f84a02abb412b9786e83d12022-12-21T17:15:29ZengNature PortfolioScientific Reports2045-23222022-03-0112111410.1038/s41598-022-08005-6Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironmentNicole N. Scheff0Ian M. Wall1Sam Nicholson2Hannah Williams3Elyssa Chen4Nguyen H. Tu5John C. Dolan6Cheng Z. Liu7Malvin N. Janal8Nigel W. Bunnett9Brian L. Schmidt10Department of Neurobiology and Hillman Cancer Research Center, University of PittsburghDepartment of Oral and Maxillofacial Surgery, Bluestone Center for Clinical Research, New York University (NYU) College of DentistryDepartment of Oral and Maxillofacial Surgery, Bluestone Center for Clinical Research, New York University (NYU) College of DentistryDepartment of Oral and Maxillofacial Surgery, Bluestone Center for Clinical Research, New York University (NYU) College of DentistryDepartment of Oral and Maxillofacial Surgery, Bluestone Center for Clinical Research, New York University (NYU) College of DentistryDepartment of Oral and Maxillofacial Surgery, Bluestone Center for Clinical Research, New York University (NYU) College of DentistryDepartment of Oral and Maxillofacial Surgery, Bluestone Center for Clinical Research, New York University (NYU) College of DentistryPathology Department, NYU Langone HealthDepartment of Epidemiology and Health Promotion, NYU College of DentistryDepartment of Molecular Pathobiology, NYU College of DentistryDepartment of Neurobiology and Hillman Cancer Research Center, University of PittsburghAbstract Oral cancer patients report sensitivity to spicy foods and liquids. The mechanism responsible for chemosensitivity induced by oral cancer is not known. We simulate oral cancer-induced chemosensitivity in a xenograft oral cancer mouse model using two-bottle choice drinking and conditioned place aversion assays. An anatomic basis of chemosensitivity is shown in increased expression of TRPV1 in anatomically relevant trigeminal ganglion (TG) neurons in both the xenograft and a carcinogen (4-nitroquinoline 1-oxide)-induced oral cancer mouse models. The percent of retrograde labeled TG neurons that respond to TRPV1 agonist, capsaicin, is increased along with the magnitude of response as measured by calcium influx, in neurons from the cancer models. To address the possible mechanism of TRPV1 sensitivity in tongue afferents, we study the role of PAR2, which can sensitize the TRPV1 channel. We show co-expression of TRPV1 and PAR2 on tongue afferents and using a conditioned place aversion assay, demonstrate that PAR2 mediates oral cancer-induced, TRPV1-evoked sensitivity in an oral cancer mouse model. The findings provide insight into oral cancer-mediated chemosensitivity.https://doi.org/10.1038/s41598-022-08005-6 |
| spellingShingle | Nicole N. Scheff Ian M. Wall Sam Nicholson Hannah Williams Elyssa Chen Nguyen H. Tu John C. Dolan Cheng Z. Liu Malvin N. Janal Nigel W. Bunnett Brian L. Schmidt Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment Scientific Reports |
| title | Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment |
| title_full | Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment |
| title_fullStr | Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment |
| title_full_unstemmed | Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment |
| title_short | Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment |
| title_sort | oral cancer induced trpv1 sensitization is mediated by par2 signaling in primary afferent neurons innervating the cancer microenvironment |
| url | https://doi.org/10.1038/s41598-022-08005-6 |
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