title: Molecular characterization of CD133+ cancer stem-like cells in endometrial cancer.
abstract: A small subset of cells with CD133 expression is thought to have increased chemoresistance and tumorigenicity, features of cancer stem cells (CSCs); the molecular mechanisms by which these properties arise remain unclear. We characterized CD133+ endometrial cancer cells based on microarray analyses of Ishikawa cells. Of the genes upregulated in CD133+ cells compared with CD133- cells, we noted several key factors involved in the aggressive behavior of cells, including ABCG2 and matrix metalloproteinase (MMP). Flow cytometric analyses identified a side-cell population (SP) with CSC features in Ishikawa cells, and they were found to be more enriched in CD133+ cells than CD133- cells. In particular, CD133+/SP cells exhibited higher proliferative and colony‑forming activity than CD133+/non-SP cells. Matrigel invasion assay revealed that CD133+ cells have enhanced invasive capacity with elevated MT1-MMP expression. siRNA‑based knockdown of MT1-MMP largely abolished the invasive capacity of CD133+ cells, but not CD133- cells due to low levels of constitutive MT1-MMP1 expression. These findings demonstrate that increased chemoresistance and tumorigenic potential of CD133+ cells are at least partly attributed to an enriched SP fraction as well as increased MMP-1 expression. These results will be of assistance in the establishment of molecular target therapy to CSCs in endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Mizumoto
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Maida
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Bono
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takakura
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
mesh_terms: D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D006023:Glycoproteins; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D053511:Matrix Metalloproteinase 14