title: Coxsackie-adenovirus receptor as a novel marker of stem cells in treatment-resistant non-small cell lung cancer.
abstract: BACKGROUND
  Treatment resistance resulting from the presence of cancer stem cells (CSCs) remains a challenge in cancer treatment. Little is known about possible markers of CSCs in treatment-resistant non-small cell lung cancer (NSCLC). We explored the coxsackie-adenovirus receptor (CAR) as one such marker of CSCs in models of treatment-resistant NSCLC.
  
  
  METHODS
  Resistant H460 and A549 cell lines were established by repeated exposure to paclitaxel or fractionated radiation. CSC markers were measured by Western blotting and flow cytometry. We also established stable CAR-overexpressing and stable shRNA-CAR-knockdown cell lines and assessed their survival, invasiveness, and tumorigenic capabilities with clonogenic, telomerase, Matrigel, and tumor formation assays.
  
  
  RESULTS
  CAR expression was associated with CSC phenotype both in vitro and in vivo. CAR-overexpressing cells were more treatment-resistant, self-renewing, and tumorigenic than were parental cells, and shRNA-mediated knockdown of CAR expression was sufficient to inhibit these functions. CAR expression also correlated with the epithelial-mesenchymal transition.
  
  
  CONCLUSIONS
  We showed for the first time that CAR is a marker of CSCs and may affect the activities of CSCs in treatment-resistant NSCLC. CAR may prove to be a target for CSC treatment and a predictor of treatment response in patients with NSCLC.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000818:Animals; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000032:analysis / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D011836:Radiation Tolerance
chemical_list: D015415:Biomarkers; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein