title: Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance.
abstract: A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, can maintain the tumor by generating differentiated cells [non-stem cells (non-CSCs)] which make up the bulk of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence. CSC identified in EOC cells isolated form ascites and solid tumors are characterized by: CD44+, MyD88+, constitutive NFkappaB activity and cytokine and chemokine production, high capacity for repair, chemoresistance to conventional chemotherapies, resistance to TNFalpha-mediated apoptosis, capacity to form spheroids in suspension, and the ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique characteristics of CSCs that control self-renewal and drive metastasis. The identification and cloning of human OCSCs can aid in the development of better therapeutic approaches for ovarian cancer patients.
authors.affiliation: Department of Obstetrics and Gynecology , Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Ayesha B
authors.initials: AB
authors.lastname: Alvero
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Han-Hsuan
authors.initials: HH
authors.lastname: Fu
authors.forename: Michele
authors.initials: M
authors.lastname: Montagna
authors.forename: Peter E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: Thomas
authors.initials: T
authors.lastname: Rutherford
authors.forename: Dan-Arin
authors.initials: DA
authors.lastname: Silasi
authors.forename: Karina D
authors.initials: KD
authors.lastname: Steffensen
authors.forename: Marianne
authors.initials: M
authors.lastname: Waldstrom
authors.forename: Irene
authors.initials: I
authors.lastname: Visintin
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D010641:Phenotype; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D018960:Hyaluronan Receptors; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4