Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models
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- Huiping Liu
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Manishkumar R. Patel
- Department of Radiology,
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- Jennifer A. Prescher
- Department of Radiology,
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- Antonia Patsialou
- Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461;
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- Dalong Qian
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Jiahui Lin
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Susanna Wen
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Ya-Fang Chang
- Department of Radiology,
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- Michael H. Bachmann
- Department of Radiology,
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- Yohei Shimono
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Piero Dalerba
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Maddalena Adorno
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Neethan Lobo
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
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- Janet Bueno
- Departments of hPathology and
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- Frederick M. Dirbas
- Surgery, Stanford University, Stanford, CA 94305;
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- Sumanta Goswami
- Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461;
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- George Somlo
- City of Hope Cancer Center, Duarte, CA 91010; and
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- John Condeelis
- Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461;
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- Christopher H. Contag
- Department of Radiology,
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- Sanjiv Sam Gambhir
- Department of Radiology,
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- Michael F. Clarke
- Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94304;
説明
<jats:p>To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44<jats:sup>+</jats:sup>cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 107 (42), 18115-18120, 2010-10-04
Proceedings of the National Academy of Sciences
