CD133+ Cancer Stem Cell–like Cells Derived from Uterine Carcinosarcoma (Malignant Mixed Müllerian Tumor)§

Authors

  • Batsuren Choijamts,

    1. Department of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan
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  • Shiro Jimi,

    1. Department of Pathology, Faculty of Medicine, School of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan
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  • Toru Kondo,

    1. Department of Stem Cell Biology, Proteo-Medicine Research Center, Ehime University, Shitsukawa, Toon, Ehime, Japan
    2. Laboratory for Morphogenetic Signaling, Center for Developmental Biology, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, Japan
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  • Yasuko Naganuma,

    1. Department of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan
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  • Taichi Matsumoto,

    1. Department of Medical System Science, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan
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  • Masahide Kuroki,

    1. Department of Biochemistry, Faculty of Medicine, School of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan
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  • Hiroshi Iwasaki,

    1. Department of Pathology, Faculty of Medicine, School of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan
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  • Makoto Emoto

    Corresponding author
    1. Department of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan
    2. Division of Gynecology, Center for Preventive Medicine, Fukuoka Sanno Hospital, International University of Health and Welfare, Momochihama, Sawara-ku, Fukuoka, Japan
    • Division of Gynecology, Center for Preventive Medicine, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45, Momochihama, Sawara-ku, Fukuoka 814-0001, Japan
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    • Telephone: 81-92-832-1100; Fax: 81-92-832-1102


  • Author contributions: B.C.: experimental procedures, conception and design, collection and assembly of data, data analysis, manuscript writing; S.J.: collection and assembly of data, data analysis and interpretation; T.K.: conception and design, manuscript writing; Y.N.: collection and assembly of data, data analysis; T.M.: experimental procedures;, M.K.: admistrative support, financial support; H.I.: collection of data, establishment of cell line; M.E.: conception and design, manuscript writing, final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS September 14, 2011.

Abstract

Cancer stem cells (CSCs) that display tumor-initiating properties have recently been identified. CD133, a surface glycoprotein linked to organ-specific stem cells, has been described as a marker of CSCs in different tumor types. We herein identify and characterize CSCs in human uterine carcinosarcoma (malignant mixed Müllerian tumor), which is one of the most aggressive and therapy-resistant gynecological malignancies and is considered to be of mesodermal origin. The CD133+ population was increased in uterine carcinosarcoma, and this population showed biphasic properties in the primary tumor. CD133+ cells predominantly formed spheres in culture and were able to differentiate into mesenchymal lineages. CD133+ cells were more resistant to cisplatin/paclitaxel-induced cytotoxicity in comparison with CD133 cells. A real-time polymerase chain reaction analysis of the genes implicated in stem cell maintenance revealed that CD133+ cells express significantly higher levels of Oct4, Nanog, Sox2, and Bmi1 than CD133 cells. Moreover, CD133+ cells showed a high expression level of Pax2 and Wnt4, which are genes essential for Müllerian duct formation. These CD133+ cells form serially transplantable tumors in vivo and the resulting CD133+ tumors replicated the EpCAM, vimentin, and estrogen and progesterone receptor expression of the parent tumor, indicating that CSCs likely differentiated into cells comprising the uterine carcinosarcoma tissue. Moreover, strong CD133 expression in both epithelial and mesenchymal elements in primary tumor demonstrated significant prognostic value. These findings suggest that CD133+ cells have the characteristics of CSCs and Müllerian mesenchymal progenitors. STEM CELLS 2011;29:1485–1495

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