A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin
(2019) In BMC Cancer 19(1).- Abstract
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... (More)
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.
(Less)
- author
- organization
-
- Division of Medical Microbiology
- Tumor microenvironment
- Molecular virology (research group)
- Aneuploidy in cancer (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Division of Clinical Genetics
- Otorhinolaryngology (Lund)
- Head and Neck Cancer Research Group (research group)
- publishing date
- 2019-03-25
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cell line, Cetuximab, Cisplatin, Human papilloma virus, Radiation, Tonsil cancer
- in
- BMC Cancer
- volume
- 19
- issue
- 1
- article number
- 265
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85063525856
- pmid:30909875
- ISSN
- 1471-2407
- DOI
- 10.1186/s12885-019-5469-8
- language
- English
- LU publication?
- yes
- id
- 4809c10b-573b-487a-b264-d6f653c62bfc
- date added to LUP
- 2019-04-08 10:01:01
- date last changed
- 2024-08-07 13:24:29
@article{4809c10b-573b-487a-b264-d6f653c62bfc, abstract = {{<p>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.</p>}}, author = {{Forslund, Ola and Sugiyama, Natsuki and Wu, Chengjun and Ravi, Naveen and Jin, Yuesheng and Swoboda, Sabine and Andersson, Fredrik and Bzhalava, Davit and Hultin, Emilie and Paulsson, Kajsa and Dillner, Joakim and Schwartz, Stefan and Wennerberg, Johan and Ekblad, Lars}}, issn = {{1471-2407}}, keywords = {{Cell line; Cetuximab; Cisplatin; Human papilloma virus; Radiation; Tonsil cancer}}, language = {{eng}}, month = {{03}}, number = {{1}}, publisher = {{BioMed Central (BMC)}}, series = {{BMC Cancer}}, title = {{A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin}}, url = {{http://dx.doi.org/10.1186/s12885-019-5469-8}}, doi = {{10.1186/s12885-019-5469-8}}, volume = {{19}}, year = {{2019}}, }