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Research Paper
Breast Cancer Metastasis in a Human Bone NOD/SCID Mouse Model
Wenyi Yang, Pearl Lam, Richard Kitching, Harriette Kahn, Albert Yee, Jane E. Aubin and Arun Seth
volume 6 | issue 8
August 2007Pages: 1289 - 1294
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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, i.e., 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 week. 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 co-transplantation of GFP-MDA-MB-231 breast cancer cells with morcellized human bone allows for tissue specific metastasis to an initially tumor free bone implant. This is in contrast to other models where the MDA-MB-231 breast cancer cells preferentially colonize the lung of host mice. 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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.