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

Journal Article · Fri Apr 01 04:00:00 EDT 2016 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2016.01.005· OSTI ID:22648611

Vlashi, Erina ^[1]; Chen, Allen M.; Boyrie, Sabrina; Yu, Garrett; Nguyen, Andrea; Brower, Philip A. ^[1]; Hess, Clayton B. ^[2]; Pajonk, Frank ^[1]

---

1. Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)
2. Department of Radiation Oncology, University of California Davis, Sacramento, California (United States)

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.

• OSTI ID: 22648611
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 94; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CHAIN REACTIONS
HEAD
IN VITRO
IN VIVO
NECK
NEOPLASMS
RADIOTHERAPY
STEM CELLS