Rat Models of Bone Metastases

Abstract

Bone metastases occur frequently in patients with advanced breast or prostate cancer. Bone metastases can be predominantly osteolytic, osteoblastic or mixed. Studies with animal models allow advances in understanding the molecular basis for bone metastases and provide new targets for therapy. Several animal models have been developed in rat with different pathophysiologies; they required injection or implantation of neoplastic cells into orthotopic locations, bones or the left ventricle of the heart. Several specific strains of rat have an increased incidence of spontaneous tumors. Carcinomas can be induced by either chemicals or physical agents. However, the most used and convenient way to induce bone metastases is a syngeneic transmission. MAT-Ly-Lu cells have been used in several models using Copenhagen rats to induce osteoblastic bone lesions. PA-III cells derived from Pollard tumors can also produce a combination of osteolytic and osteoblastic reactions at the site of transplantation. Osteolytic bone lesions can be obtained with an injection of Walker cells. The use of 13762 or c-SST2 cells allows also leads to osteolysis. Human xenografts can only be used in nude animals. It is essential to validate and correctly interpret the lesions in several models of bone metastasis. No animal model is sufficient by itself to represent the clinical findings observed in humans. The use of models developed in different species should be more predictive and bring a beam of arguments for a better knowledge of pathophysiological and therapeutic mechanisms.