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A Mouse Model of Human Breast Cancer Metastasis to Human Bone

¹ Tufts University School of Medicine; ² Department of Anatomy/Cell Biology and Radiation Oncology, Tufts University School of Medicine, Tufts-New England Medical Center-Molecular Oncology Research Institute; ³ Department of Pathology, Tufts-New England Medical Center; ⁴ Department of Orthopedics, New England Baptist Hospital, Boston, Massachusetts; ⁵ Mount Auburn Hospital; ⁶ Whitehead Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts; and ⁷ J Cardeza Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, Pennsylvania

Requests for reprints: Charlotte Kuperwasser, Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Jaharis 701, Boston, MA 02111. Phone: 617-636-2908; Fax: 617-636-0445; E-mail: Charlotte.Kuperwasser{at}tufts.edu.

Currently, an in vivo model of human breast cancer metastasizing from the orthotopic site to bone does not exist, making it difficult to study the many steps of skeletal metastasis. Moreover, models used to identify the mechanisms by which breast cancer metastasizes to bone are limited to intracardiac injection, which seeds the cancer cells directly into the circulation, thus bypassing the early steps in the metastatic process. Such models do not reflect the full process of metastasis occurring in patients. We have developed an animal model of breast cancer metastasis in which the breast cancer cells and the bone target of osteotropic metastasis are both of human origin. The engrafted human bone is functional, based on finding human IgG in the mouse bloodstream, human B cells in the mouse spleen, and normal bone histology. Furthermore, orthotopic injection of a specific human breast cancer cell line, SUM1315 (derived from a metastatic nodule in a patient), later resulted in both bone and lung metastases. In the case of bone, metastasis was to the human implant and not the mouse skeleton, indicating a species-specific osteotropism. This model replicates the events observed in patients with breast cancer skeletal metastases and serves as a useful and relevant model for studying the disease.

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