title: Therapy-resistant cancer stem cells have differing sensitivity to photon versus proton beam radiation.
abstract: BACKGROUND
  Cancer stem cells (CSCs) play an important role in non-small-cell lung cancer recurrence and metastasis. We sought to determine whether CSC-like cells respond differentially to proton and photon beam therapies.
  
  
  METHODS
  CSC-enriched cells from paclitaxel-resistant human H460 and A549 cell lines were irradiated with the same relative biological effectiveness dose and analyzed for cell viability, clonogenic survival, apoptosis, cell migration, cell invasiveness, tumor sphere formation, and CSC markers. The intracellular concentration of reactive oxygen species (ROS) was measured before and after irradiation.
  
  
  RESULTS
  Compared with photons, protons caused significantly lower cell viability in chemoresistant cells and, in CSC-like cells, significantly lower clonogenic survival, invasiveness, and number of tumor spheres; less migration and CSC markers (coxsackievirus and adenovirus receptor, β-catenin, and side population cells); more apoptosis; and higher ROS level. CSC-like cells contained less than half the ROS levels of parental cancer cells or normal human bronchial epithelial cells.
  
  
  CONCLUSIONS
  CSC-like cells may be more sensitive to irradiation with protons than photons. The increased sensitivity could be caused by the greater ROS generated by protons. Because chemoresistant CSCs play an important role in tumor recurrence, protons may be more effective than photons in eliminating recurrent or persistent non-small-cell lung cancer.
authors.affiliation: Departments of *Radiation Oncology, †Thoracic and Cardiovascular Surgery, and ‡Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.forename: Steven H
authors.initials: SH
authors.lastname: Lin
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
authors.forename: Michael
authors.initials: M
authors.lastname: Gillin
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects*; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D017239:Paclitaxel / Q000494:pharmacology*; D017785:Photons; D011522:Protons; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011522:Protons; D017382:Reactive Oxygen Species; D017239:Paclitaxel