Breast cancer metastasis in a human bone NOD/SCID mouse model.
A major dilemma facing patients with breast cancer is how to decide between over treating indolent tumors and failing to adequately treat aggressive, potentially lethal cancers. Determination of the metastatic potential of a patient's breast cancer would clearly help guide those treatment decisions. Breast cancer commonly spreads to bone in 70% of women with advanced disease. However, the mechanism of bone metastasis is not well understood. One possibility is that the microenvironment within bone marrow, highly rich in growth factors and cytokines, is suitable for the proliferation of breast cancer cells. In this study, we developed a method for implanting human bone in NOD/SCID mice and show that the human bone implants are viable for more than 20 weeks. This human bone NOD/SCID mouse model provides an opportunity to functionally characterize human breast cancer cell behavior in an in vivo human microenvironment. Several breast tumor cell lines have been shown to grow in the human-bone-NOD/SCID model system, however each line has a different functional profile. Here we show that cotransplantation of GFP-MDA-MB-231 breast cancer cells with morcellized human bone allows for tissue specific metastasis to an initially tumor free bone implant. Furthermore, metastasis of breast tumor cells to implanted tumor-free human bone was seen when patient bone containing a metastatic breast tumor was implanted in the host mouse. With this model, we can distinguish between primary invasive breast tumors with and without bone metastatic potential.
Yang
Wenyi
W
Division of Molecular and Cellular Biology, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
Lam
Pearl
P
Kitching
Richard
R
Kahn
Harriette J
HJ
Yee
Albert
A
Aubin
Jane E
JE
Seth
Arun
A
D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation