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.

Pharmacologic inhibitors of IκB kinase suppress growth and migration of mammary carcinosarcoma cellsin vitroand prevent osteolytic bone metastasisin vivo

“…We investigated the effects of IKK inhibitors on osteolytic bone metastases using the rat W256 model of osteolytic bone metastases as described in Blouin et al (20). Briefly, 36 male Wistar rats received intracardiac injection of W256 tumor cells (10 7 cells) followed by i.p.…”

“…In view of this, pharmacologic inhibitors of IKKα and IKKβ might be expected to be of particular value in the prevention of osteolytic disease, but the effects of IKK inhibitors on bone metastases have not been previously investigated. Here, we investigated the effects of these inhibitors in a well-established model of metastatic bone disease associated with breast cancer induced by intracardiac injection of W256 mammary carcinosarcoma cells (20,21).…”

Interactions between microenvironment and cancer cells in two animal models of bone metastasis

“…Walker 256/B cells The Walker 256/B (W256) cells (issued of a rat mammary carcinoma) are associated with osteolytic metastases (Wingen et al, 1986;Rizzoli and Fleisch, 1987;Blouin et al, 2005). W256 cells (kindly provided by Pr R Rizzoli, Geneva, Switzerland) were grown in Dulbecco's modified Eagle's medium (DMEM; Eurobio, Les Ulis, France) containing 10% heat-inactivated fetal calf serum (FCS; Seromed Biochrom, Berlin, Germany), 100 UI ml À1 of penicillin (Eurobio), 100 mg ml À1 of streptomycin sulphate (Eurobio), 1% of non essential amino acids (NEAA; Cambrex, Walkersville, MD, USA) and 1 mM of sodium pyruvate (Eurobio).…”

Animal Models of Cancer Pain

“…16,31 To investigate metastatic bone cancer, MDA-MB231 human breast cancer cells (5 × 10 5 in 1 ml) were injected into the femoral arteries of nude rats. 12 Osteolytic lesions occurred exclusively in the femur, tibia, and fibula of these animals, and if the tumor cells were preincubated with an antibody against bone sialoprotein, osteolytic lesion size was reduced significantly.…”