A tale of mice and (wo)men: development of and insights from an "all human" animal model of breast cancer metastasis to bone.

There are 200,000 new cases of breast cancer (BrCa) annually in the United States. Metastasis to bone signals a life-threatening phase of this disease. Little progress has been made in understanding the pathogenesis of metastasis. Few validated drug targets have been identified. So there is a compelling need to understand the molecular mechanisms by which BrCa metastasizes to bone (osteotropism). There is need for animal models that reflect the complex biology of metastasis in humans. We performed research designed to elucidate the mechanisms of osteotropism from both sides of the tumor-stroma interface. We created an "all human" model in which human bone is transplanted into non-obese diabetic/severe combined immunodeficient immunodeficient (NOD/SCID) mice. Human BrCa cells injected into the mammary fat pad later metastasize to bone. We also found traffic in the opposite direction: bone marrow stem cells migrate from human bone to human breast tumors in the mouse. We are identifying osteotropism genes used by BrCa to metastasize to human bone.