Spontaneous Colonization of Osteoblastic Prostate Cancer Cells In Vivo: A New Model of Metastasis to Bone

Abstract

There are few models available to study spontaneous osteoblastic prostate cancer metastasis to bone. Current models require orthotopic injection and more than six months to form metastases in bone, while intracardiac injection, specifically with PC-3 cells, results only in osteoclastic bone metastases. We have hypothesized that differences in bone turnover between mice and humans is the main limitation for the spontaneous and rapid colonization of marrow forming bone by osteoblastic prostate cancer cells, as bone turnover rates in adult mice do not mimic the higher, continuous turnover rates observed in humans. SCID/bg mice were subjected to two and three week periods of tail suspension to enhance bone turnover, followed by intracardiac injection of C4-2 prostate cancer cells and a return to normal weight bearing activity. MicroCT analysis revealed a significant reduction in trabecular bone volume and an increased porosity in the femurs of tail-suspended mice relative to controls. After three weeks of tail suspension and six weeks post C4-2 cell injection, 100% of the mice demonstrated detectable serum PSA levels. Immunohistochemical staining of femurs for PSA revealed the localization of PSA positive, C4-2 cells in marrow and trabecular spaces. These results suggest that this novel model combining tail suspension in an immune compromised mouse strain and intracardiac injection could allow for the direct testing of therapeutic agents that interfere with the process of osteoblastic prostate cancer colonization of bone. Funding provided by the Howard Hughes Medical Institute and University of Delaware Research Foundation.