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A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin

BACKGROUND: Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development. METHODS: Fresh samples from 23 HPV-positive tonsil carcinomas were cult...

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Autores principales: Forslund, Ola, Sugiyama, Natsuki, Wu, Chengjun, Ravi, Naveen, Jin, Yuesheng, Swoboda, Sabine, Andersson, Fredrik, Bzhalava, Davit, Hultin, Emilie, Paulsson, Kajsa, Dillner, Joakim, Schwartz, Stefan, Wennerberg, Johan, Ekblad, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434888/
https://www.ncbi.nlm.nih.gov/pubmed/30909875
http://dx.doi.org/10.1186/s12885-019-5469-8
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author Forslund, Ola
Sugiyama, Natsuki
Wu, Chengjun
Ravi, Naveen
Jin, Yuesheng
Swoboda, Sabine
Andersson, Fredrik
Bzhalava, Davit
Hultin, Emilie
Paulsson, Kajsa
Dillner, Joakim
Schwartz, Stefan
Wennerberg, Johan
Ekblad, Lars
author_facet Forslund, Ola
Sugiyama, Natsuki
Wu, Chengjun
Ravi, Naveen
Jin, Yuesheng
Swoboda, Sabine
Andersson, Fredrik
Bzhalava, Davit
Hultin, Emilie
Paulsson, Kajsa
Dillner, Joakim
Schwartz, Stefan
Wennerberg, Johan
Ekblad, Lars
author_sort Forslund, Ola
collection PubMed
description BACKGROUND: Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development. METHODS: Fresh samples from 23 HPV-positive tonsil carcinomas were cultivated in vitro. The established cell line was analyzed for viral characteristics, cell karyotype, TP53 status, and growth capabilities in nude mice. In vitro studies of sensitivities to radiation, cisplatin and cetuximab were performed. RESULTS: After 19 months (eight passages), one cell line, LU-HNSCC-26, was established in vitro and also grew as xenografts. The tumor was from a 48 year old non-smoking man with non-keratinizing, p16 positive tonsil OSCC, stage T2N0M0 with HPV16. It contained 19.5 (CV% 3.7) HPV16 copies/cell (passage 8). The complete HPV16 genome sequence was obtained. Episomal HPV16 was present with an E2/E7 ratio of 1.1 (CV% 2.6). In addition, HPV16 mRNA specific for the intact E2 gene was detected. The viral expression manifested 1.0 (CV% 0.1) E7 mRNA copies per HPV16 genome. The karyotype was determined and the cell line demonstrated wild type TP53. The ID50 for radiation was 0.90 Gy and the IC50 for cisplatin was 0.99 μmol/L. The cell line was inhibited to a maximum of 18% by cetuximab. CONCLUSIONS: We established an in vitro tonsil carcinoma cell line containing episomal HPV16. This is an important step towards efficient treatment development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5469-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-64348882019-04-08 A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin Forslund, Ola Sugiyama, Natsuki Wu, Chengjun Ravi, Naveen Jin, Yuesheng Swoboda, Sabine Andersson, Fredrik Bzhalava, Davit Hultin, Emilie Paulsson, Kajsa Dillner, Joakim Schwartz, Stefan Wennerberg, Johan Ekblad, Lars BMC Cancer Research Article BACKGROUND: Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development. METHODS: Fresh samples from 23 HPV-positive tonsil carcinomas were cultivated in vitro. The established cell line was analyzed for viral characteristics, cell karyotype, TP53 status, and growth capabilities in nude mice. In vitro studies of sensitivities to radiation, cisplatin and cetuximab were performed. RESULTS: After 19 months (eight passages), one cell line, LU-HNSCC-26, was established in vitro and also grew as xenografts. The tumor was from a 48 year old non-smoking man with non-keratinizing, p16 positive tonsil OSCC, stage T2N0M0 with HPV16. It contained 19.5 (CV% 3.7) HPV16 copies/cell (passage 8). The complete HPV16 genome sequence was obtained. Episomal HPV16 was present with an E2/E7 ratio of 1.1 (CV% 2.6). In addition, HPV16 mRNA specific for the intact E2 gene was detected. The viral expression manifested 1.0 (CV% 0.1) E7 mRNA copies per HPV16 genome. The karyotype was determined and the cell line demonstrated wild type TP53. The ID50 for radiation was 0.90 Gy and the IC50 for cisplatin was 0.99 μmol/L. The cell line was inhibited to a maximum of 18% by cetuximab. CONCLUSIONS: We established an in vitro tonsil carcinoma cell line containing episomal HPV16. This is an important step towards efficient treatment development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5469-8) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-25 /pmc/articles/PMC6434888/ /pubmed/30909875 http://dx.doi.org/10.1186/s12885-019-5469-8 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Forslund, Ola
Sugiyama, Natsuki
Wu, Chengjun
Ravi, Naveen
Jin, Yuesheng
Swoboda, Sabine
Andersson, Fredrik
Bzhalava, Davit
Hultin, Emilie
Paulsson, Kajsa
Dillner, Joakim
Schwartz, Stefan
Wennerberg, Johan
Ekblad, Lars
A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
title A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
title_full A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
title_fullStr A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
title_full_unstemmed A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
title_short A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
title_sort novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434888/
https://www.ncbi.nlm.nih.gov/pubmed/30909875
http://dx.doi.org/10.1186/s12885-019-5469-8
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