title: Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm.
abstract: The lack of significant progress in the treatment of epithelial ovarian cancer (EOC) underscores the need to gain a better understanding of the processes that lead to chemoresistance and recurrence. The cancer stem cell (CSC) hypothesis offers an attractive explanation of how a subpopulation of cells within a patient's tumour might remain refractory to treatment and subsequently form the basis of recurrent chemoresistant disease. This review examines the literature defining somatic stem cells of the ovary and fallopian tube, two tissues that give rise to EOC. In addition, considerable research has been reviewed, that has identified subpopulations of EOC cells, based on marker expression (CD133, CD44, CD117, CD24, epithelial cell adhesion molecule, LY6A, ALDH1 and side population (SP)), which are enriched for tumour initiating cells (TICs). While many studies identified either CD133 or CD44 as markers useful for enriching for TICs, there is little consensus. This suggests that EOC cells may have a phenotypic plasticity that may preclude the identification of universal markers defining a CSC. The assay that forms the basis of quantifying TICs is the xenograft assay. Considerable controversy surrounds the xenograft assay and it is essential that some of the potential limitations be examined in this review. Highlighting such limitations or weaknesses is required to properly evaluate data and broaden our interpretation of potential mechanisms that might be contributing to the pathogenesis of ovarian cancer.
authors.affiliation: Ottawa Hospital Research InstituteCentre for Cancer Therapeutics, Ottawa, Ontario, Canada K1H 8L6Department of Cellular and Molecular MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Garson
authors.affiliation: Ottawa Hospital Research InstituteCentre for Cancer Therapeutics, Ottawa, Ontario, Canada K1H 8L6Department of Cellular and Molecular MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 Ottawa Hospital Research InstituteCentre for Cancer Therapeutics, Ottawa, Ontario, Canada K1H 8L6Department of Cellular and Molecular MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 bvanderhyden@ohri.ca.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Vanderhyden
mesh_terms: D000071916:AC133 Antigen; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D000077216:Carcinoma, Ovarian Epithelial; D019008:Drug Resistance, Neoplasm; D005187:Fallopian Tubes / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D009364:Neoplasm Recurrence, Local; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D010053:Ovary / Q000473:pathology; D010455:Peptides / Q000032:analysis; D050697:Retinal Dehydrogenase / Q000032:analysis; D013234:Stem Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D007527:Isoenzymes; C000606023:PROM1 protein, human; D010455:Peptides; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase