A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells

A new model for the study of spontaneous bone metastasis has been developed which allows for the quantification of metastatic tumor burden and cancer cell growth rate, and which describes the progressive changes in bone morphology. Walker 256 (W256) cells or vehicle were injected into the left upper thigh muscle of male Fischer rats, which were killed 7, 10 or 14 days later. By day 7, metastases had appeared in the distal femur, in the glomeruli of the kidney, and diffusely throughout the liver and lungs. The extent of tumor burden in these organs increased over time. In the femur, 14 days of tumor burden was associated with a 53 ± 10% decrease in trabecular bone content, a 61 ± 15% increase in osteoclast surface, and a 95 ± 10% decrease in osteoblast surface, as compared with non-tumor-bearing controls. By autoradiography, metastatic tumor cells in all organs were determined to have greater growth rates than did cells in the primary tumor. However, within the femur, W256 cells located adjacent to trabecular bone surfaces had a 33 ± 7% greater growth rate than did W256 cells located >50 µm from bone surfaces (P < 0.05), suggesting a mitogenic effect of bone.