CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer§

Authors

  • Michael D. Curley,

    1. Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts
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  • Vanessa A. Therrien,

    1. Harvard Stem Cell Institute, Cambridge, Massachusetts
    2. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts
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  • Christine L. Cummings,

    1. Harvard Stem Cell Institute, Cambridge, Massachusetts
    2. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts
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  • Petra A. Sergent,

    1. Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts
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  • Carolyn R. Koulouris,

    1. Harvard Stem Cell Institute, Cambridge, Massachusetts
    2. Gynecologic Oncology Division, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts
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  • Anne M. Friel,

    1. Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts
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  • Drucilla J. Roberts,

    1. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
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  • Michael V. Seiden,

    1. Fox Chase Cancer Center, Philadelphia, Pennsylvania
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  • David T. Scadden,

    1. Harvard Stem Cell Institute, Cambridge, Massachusetts
    2. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts
    3. MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts
    4. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts
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  • Bo R. Rueda,

    1. Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts
    2. Harvard Stem Cell Institute, Cambridge, Massachusetts
    3. Gynecologic Oncology Division, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts
    4. MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts
    5. Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts
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  • Rosemary Foster

    Corresponding author
    1. Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts
    2. Harvard Stem Cell Institute, Cambridge, Massachusetts
    3. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts
    4. MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts
    5. Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts
    • Vincent Center for Reproductive Biology, Thier 901, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA
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    • Telephone: 617-724-9619; Fax: 617-726-0561


  • Author contributions: M.D.C.: Collection and assembly of data, data analysis and interpretation, manuscript writing; V.A.T. and C.L.C.: Collection and assembly of data; P.A.S.: Provision of study material; C.R.K.: Provision of study material; A.M.F.: Collection and assembly of data, data analysis and interpretation; D.J.R.: Data analysis and interpretation; M.V.S.: Conception and design, financial support, provision of study material or patients; D.T.S.: Financial support, data analysis and interpretation; B.R.R.: Conception and design, financial support, provision of study material and patients, data analysis and interpretation, manuscript writing; R.F.: Conception and design, financial support, provision of study material or patients, data analysis and interpretation, manuscript writing, final approval of manuscript.

  • First published online in STEM CELLS EXPRESS October 8, 2009.

  • §

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

Abstract

Evidence is accumulating that solid tumors contain a rare phenotypically distinct population of cells, termed cancer stem cells (CSC), which give rise to and maintain the bulk of the tumor. These CSC are thought to be resistant to current chemotherapeutic strategies due to their intrinsic stem-like properties and thus may provide the principal driving force behind recurrent tumor growth. Given the high frequency of recurrent metastasis associated with human ovarian cancer, we sought to determine whether primary human ovarian tumors contain populations of cells with enhanced tumor-initiating capacity, a characteristic of CSC. Using an in vivo serial transplantation model, we show that primary uncultured human ovarian tumors can be reliably propagated in NOD/SCID mice, generating heterogeneous tumors that maintain the histological integrity of the parental tumor. The observed frequency of tumor engraftment suggests only certain subpopulations of ovarian tumor cells have the capacity to recapitulate tumor growth. Further profiling of human ovarian tumors for expression of candidate CSC surface markers indicated consistent expression of CD133. To determine whether CD133 expression could define a tumor-initiating cell population in primary human ovarian tumors, fluorescence-activated cell sorting (FACS) methods were employed. Injection of sorted CD133+ and CD133 cell populations into NOD/SCID mice established that tumor-derived CD133+ cells have an increased tumorigenic capacity and are capable of recapitulating the original heterogeneous tumor. Our data indicate that CD133 expression defines a NOD/SCID tumor initiating subpopulation of cells in human ovarian cancer that may be an important target for new chemotherapeutic strategies aimed at eliminating ovarian cancer. STEM CELLS 2009;27:2875–2883

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