A metastatic human prostate cancer model using intraprostatic implantation of tumor produced by PC-3 neolacZ transfected cells.

The purpose of this study was to develop a model that investigates the biology of prostate cancer (PCA) that is metastatic to the bone, while closely approximates the clinical presentation of this disease. Human prostate cancer PC-3 cells were transfected with the neolacZ retrovirus. Then, eight-week-old SCID mice were injected subcutaneously with a single dose of PC-3 neolacZ cells. When the mice developed tumors at the injection site, they were sacrificed to harvest tumor fragments. One tumor fragment from a single PC-3 neolacZ injected animal was implanted into the prostates of five SCID mice. The SCID mice had all been previously grafted with adult human bone. Mice were sacrificed and tumor growth and metastasis to murine tissues as well as to the human bone graft were sought. The histologic samples were stained with X-Gal. In three mice tumors metastasized to the skeletal system. One animal showed limited X-Gal staining of the cells surrounding the human bone implant. In two mice tumors metastasized to liver and kidney and one metastasized to the lung. In this study we established a spontaneous bone metastasis model of human PCA cells with the combination of lacZ expression and orthotopic implantation of the PC-3 implanted tumor fragments. This model offers potential advantages in monitoring the metastatic pattern and behavior of prostate cancer and may be used to selectively study its interaction with human bone.