title: Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells.
abstract: Identification of cancer stem cells is crucial for advancing cancer biology and therapy. Several markers including CD24, CD44, CD117, CD133, the G subfamily of ATP-binding cassette transporters (ABCG), epithelial specific antigen (ESA) and aldehyde dehydrogenase (ALDH) are used to identify and investigate human epithelial cancer stem cells in the literature. We have now systemically analyzed and compared the expression of these markers in fresh ovarian epithelial carcinomas. Although the expression levels of these markers were unexpectedly variable and partially overlapping in fresh ovarian cancer cells from different donors, we reliably detected important levels of CD133 and ALDH in the majority of fresh ovarian cancer. Furthermore, most of these stem cell markers including CD133 and ALDH were gradually lost following in vitro passage of primary tumor cells. However, the expression of ALDH and CD133, but not CD24, CD44 and CD117, could be partially rescued by the in vitro serum-free and sphere cultures and by the in vivo passage in the immune-deficient xenografts. ALDH+ and CD133+ cells formed three-dimensional spheres more efficiently than their negative counterparts. These sphere-forming cells expressed high levels of stem cell core gene transcripts and could be expanded and form additional spheres in long-term culture. ALDH+ , CD133+ and ALDH+ CD133+ cells from fresh tumors developed larger tumors more rapidly than their negative counterparts. This property was preserved in the xenografted tumors. Altogether, the data suggest that ALDH+ and CD133+ cells are enriched with ovarian cancer-initiating (stem) cells and that ALDH and CD133 may be widely used as reliable markers to investigate ovarian cancer stem cell biology.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI 48109-0669, USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kryczek
authors.forename: Suling
authors.initials: S
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: Roh
authors.forename: Linhua
authors.initials: L
authors.lastname: Vatan
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szeliga
authors.forename: Shuang
authors.initials: S
authors.lastname: Wei
authors.forename: Mousumi
authors.initials: M
authors.lastname: Banerjee
authors.forename: Yujun
authors.initials: Y
authors.lastname: Mao
authors.forename: Jan
authors.initials: J
authors.lastname: Kotarski
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.forename: Rebecca
authors.initials: R
authors.lastname: Liu
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
mesh_terms: D000071916:AC133 Antigen; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C115572:ABCD1 protein, human; D000071916:AC133 Antigen; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse