期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 42, 页码 18115-18120出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1006732107
关键词
breast cancer; human-in-mouse cancer models; fused optical reporters; bioluminescence imaging
资金
- National Institutes of Health (NIH) [U54 CA 126524, P01 CA139490]
- Breast Cancer Research Foundation
- NIH [T90, M01RR00043]
- Department of Defense [BC087695]
- University of Chicago
- National Cancer Institute (NCI) In Vivo Cellular and Molecular Imaging Centers [P50 CA114747]
- Komen Foundation
- NCI [R25T, R01 CA113395, U54 CA126511, CA 33572]
- California Breast Cancer Research Program
- Breast Cancer Alliance
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(+) 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.
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