skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status

Abstract

Purpose: To test the hypothesis that the radiation response of cancer stem cells (CSCs) in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) differs and is not reflected in the radiation response of the bulk tumor populations, that radiation therapy (RT) can dedifferentiate non-stem HNSCC cells into CSCs, and that radiation-induced dedifferentiation depends on the HPV status. Methods and Materials: Records of a cohort of 162 HNSCC patients were reviewed, and their outcomes were correlated with their HPV status. Using a panel of HPV-positive and HPV-negative HNSCC cell lines expressing a reporter for CSCs, we characterized HPV-positive and HPV-negative lines via flow cytometry, sphere-forming capacity assays in vitro, and limiting dilution assays in vivo. Non-CSCs were treated with different doses of radiation, and the dedifferentiation of non-CSCs into CSCs was investigated via flow cytometry and quantitative reverse transcription–polymerase chain reaction for re-expression of reprogramming factors. Results: Patients with HPV-positive tumors have superior overall survival and local–regional control. Human papillomavirus–positive HNSCC cell lines have lower numbers of CSCs, which inversely correlates with radiosensitivity. Human papillomavirus–negative HNSCC cell lines lack hierarchy owing to enhanced spontaneous dedifferentiation. Non-CSCs from HPV-negative lines show enhanced radiation-induced dedifferentiation compared with HPV-positive lines, and RT inducedmore » re-expression of Yamanaka reprogramming factors. Conclusions: Supporting the favorable prognosis of HPV-positive HNSCCs, we show that (1) HPV-positive HNSCCs have a lower frequency of CSCs; (2) RT can dedifferentiate HNSCC cells into CSCs; and (3) radiation-induced dedifferentiation depends on the HPV status of the tumor.« less

Authors:
 [1];  [2]; ; ; ; ;  [1];  [3];  [1];  [2]
  1. Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)
  2. (United States)
  3. Department of Radiation Oncology, University of California Davis, Sacramento, California (United States)
Publication Date:
OSTI Identifier:
22648611
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 94; Journal Issue: 5; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHAIN REACTIONS; HEAD; IN VITRO; IN VIVO; NECK; NEOPLASMS; RADIOTHERAPY; STEM CELLS

Citation Formats

Vlashi, Erina, E-mail: evlashi@mednet.ucla.edu, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California, Chen, Allen M., Boyrie, Sabrina, Yu, Garrett, Nguyen, Andrea, Brower, Philip A., Hess, Clayton B., Pajonk, Frank, and Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California. Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.01.005.
Vlashi, Erina, E-mail: evlashi@mednet.ucla.edu, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California, Chen, Allen M., Boyrie, Sabrina, Yu, Garrett, Nguyen, Andrea, Brower, Philip A., Hess, Clayton B., Pajonk, Frank, & Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California. Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status. United States. doi:10.1016/J.IJROBP.2016.01.005.
Vlashi, Erina, E-mail: evlashi@mednet.ucla.edu, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California, Chen, Allen M., Boyrie, Sabrina, Yu, Garrett, Nguyen, Andrea, Brower, Philip A., Hess, Clayton B., Pajonk, Frank, and Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California. Fri . "Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status". United States. doi:10.1016/J.IJROBP.2016.01.005.
@article{osti_22648611,
title = {Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status},
author = {Vlashi, Erina, E-mail: evlashi@mednet.ucla.edu and Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California and Chen, Allen M. and Boyrie, Sabrina and Yu, Garrett and Nguyen, Andrea and Brower, Philip A. and Hess, Clayton B. and Pajonk, Frank and Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California},
abstractNote = {Purpose: To test the hypothesis that the radiation response of cancer stem cells (CSCs) in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) differs and is not reflected in the radiation response of the bulk tumor populations, that radiation therapy (RT) can dedifferentiate non-stem HNSCC cells into CSCs, and that radiation-induced dedifferentiation depends on the HPV status. Methods and Materials: Records of a cohort of 162 HNSCC patients were reviewed, and their outcomes were correlated with their HPV status. Using a panel of HPV-positive and HPV-negative HNSCC cell lines expressing a reporter for CSCs, we characterized HPV-positive and HPV-negative lines via flow cytometry, sphere-forming capacity assays in vitro, and limiting dilution assays in vivo. Non-CSCs were treated with different doses of radiation, and the dedifferentiation of non-CSCs into CSCs was investigated via flow cytometry and quantitative reverse transcription–polymerase chain reaction for re-expression of reprogramming factors. Results: Patients with HPV-positive tumors have superior overall survival and local–regional control. Human papillomavirus–positive HNSCC cell lines have lower numbers of CSCs, which inversely correlates with radiosensitivity. Human papillomavirus–negative HNSCC cell lines lack hierarchy owing to enhanced spontaneous dedifferentiation. Non-CSCs from HPV-negative lines show enhanced radiation-induced dedifferentiation compared with HPV-positive lines, and RT induced re-expression of Yamanaka reprogramming factors. Conclusions: Supporting the favorable prognosis of HPV-positive HNSCCs, we show that (1) HPV-positive HNSCCs have a lower frequency of CSCs; (2) RT can dedifferentiate HNSCC cells into CSCs; and (3) radiation-induced dedifferentiation depends on the HPV status of the tumor.},
doi = {10.1016/J.IJROBP.2016.01.005},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 5,
volume = 94,
place = {United States},
year = {2016},
month = {4}
}