title: Cancer initiating-cells are enriched in the CA9 positive fraction of primary cervix cancer xenografts.
abstract: Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied. Analyses of the expression of the stem cell markers Oct4, Notch1, Sca-1 & Bmi1 showed a trend toward an increase in the CA9+ populations, albeit not significant. We present evidence that enhanced autophagy does not play a role in the enhanced growth of the CA9+ cells. Our study suggests a direct in vivo functional link between hypoxic cells and CICs in primary cervix cancer xenografts.
authors.affiliation: Ontario Cancer Institute/Princess Margaret Cancer Centre, University Health Network and Campbell Family Institute for Cancer Research, Toronto, Ontario, M5G2M9, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Delphine Tamara
authors.initials: DT
authors.lastname: Marie-Egyptienne
authors.affiliation: Ontario Cancer Institute/Princess Margaret Cancer Centre, University Health Network and Campbell Family Institute for Cancer Research, Toronto, Ontario, M5G2M9, Canada.
authors.forename: Naz
authors.initials: N
authors.lastname: Chaudary
authors.affiliation: Ontario Cancer Institute/Princess Margaret Cancer Centre, University Health Network and Campbell Family Institute for Cancer Research, Toronto, Ontario, M5G2M9, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tuula
authors.initials: T
authors.lastname: Kalliomäki
authors.affiliation: Ontario Cancer Institute/Princess Margaret Cancer Centre, University Health Network and Campbell Family Institute for Cancer Research, Toronto, Ontario, M5G2M9, Canada.|Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, M5G2M9, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David William
authors.initials: DW
authors.lastname: Hedley
authors.affiliation: Ontario Cancer Institute/Princess Margaret Cancer Centre, University Health Network and Campbell Family Institute for Cancer Research, Toronto, Ontario, M5G2M9, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Richard Peter
authors.initials: RP
authors.lastname: Hill
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
chemical_list: D000951:Antigens, Neoplasm; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX
keywords: carbonic anhydrase 9; cervix cancer; hypoxia; stem cells; xenogratfs