title: Possible association between stem-like hallmark and radioresistance in human cervical carcinoma cells.
abstract: OBJECTIVE
  We aimed to investigate the possibility of an association between a stem-like hallmark and radiotherapeutic sensitivity in human cervical carcinoma cells.
  
  
  METHODS
  Side-population (SP) cells and non-SP (NSP) cells in HeLa cells were isolated using flow cytometry and Hoechst 33342 efflux. We performed Western blot analysis to evaluate the expression of stem cell markers (CXCR4, Oct3/4, CD133, and SOX2) and apoptosis markers after irradiation. In addition, SP and NSP cells were injected into nude mice and we assessed subcutaneous tumor formation. To examine tolerance of irradiation, colony formation and apoptosis change were confirmed in the SP and NSP cells.
  
  
  RESULTS
  SP cells showed a higher expression of CXCR4, Oct3/4, CD133, and SOX2 than NSP cells. The colony size of SP cells cultured on non-coated dishes was larger than that of NSP cells, and NSP cells were easily induced to undergo apoptosis. SP cells tended to form spheroids and showed a higher level of tumorigenicity compared with NSP cells. In addition, nude mice inoculated with SP cells showed greater tumor growth compared with NSP cells. SP cells showed a higher tumorigenicity and lower apoptotic potential, leading to enhanced radiotolerance.
  
  
  CONCLUSIONS
  Tumor SP cells showed higher-level stem-cell-like characters and radioresistance than NSP cells. SP cells may be useful for new therapeutic approaches for radiation-resistant cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kumazawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Umezu
authors.forename: Mika
authors.initials: M
authors.lastname: Mizuno
authors.forename: Shiro
authors.initials: S
authors.lastname: Suzuki
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mitsui
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sekiya
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000528:radiation effects; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D011836:Radiation Tolerance; D058985:Side-Population Cells / Q000473:pathology* / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: apoptosis; cancer stem-like cell; cervical carcinoma; colony formation; radioresistance; side population