Animal models of bone metastasis

• Published in: Cancer 2003-02, Vol.97 (S3), p.748-757
• Main Authors: Rosol, Thomas J., Tannehill‐Gregg, Sarah H., LeRoy, Bruce E., Mandl, Stefanie, Contag, Christopher H.
• Format: Article
• Language: English
• Subjects: animal model; Animals; Biological and medical sciences; bone metastasis; Bone Neoplasms - diagnostic imaging; Bone Neoplasms - secondary; breast carcinoma; Disease Models, Animal; Diseases of the osteoarticular system; dog; Dogs; Female; imaging; Luminescent Measurements; Male; Mammary Neoplasms, Experimental - etiology; Mammary Neoplasms, Experimental - pathology; Medical sciences; Mice; mouse; Neoplasm Transplantation; osteoblastic metastasis; prostate carcinoma; Prostatic Neoplasms - etiology; Prostatic Neoplasms - pathology; Radiography; rat; Rats; Tumor Cells, Cultured; Tumors of striated muscle and skeleton
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.11150

BACKGROUND Animal models are important tools to investigate the pathogenesis and develop treatment strategies for bone metastases in humans. However, there are few spontaneous models of bone metastasis despite the fact that rodents (rats and mice) and other animals (dogs and cats) often spontaneously develop cancer. Therefore, most experimental models of bone metastasis in rodents require injection or implantation of neoplastic cells into orthotopic locations, bones, or the left ventricle of the heart. METHODS The current study reviews the natural incidence and clinical manifestation of bone metastases of mammary and prostate carcinoma in animals, as well as the experimental models developed in mice using animal and human‐derived neoplasms. RESULTS Rats, mice, dogs, and cats often develop spontaneous mammary carcinoma, but bone metastases are rare. Intact and neutered dogs develop prostate carcinoma that is usually androgen independent and may be associated with regional bone invasion or distant bone metastasis. Normal dog prostate tissue induces new bone formation in vivo and can serve as a model of osteoblastic metastasis without concurrent bone destruction. Experimental models of osteolytic, osteoblastic, and mixed osteolytic/osteoblastic bone metastases include syngeneic rodent neoplasms or human xenografts implanted at orthotopic sites (e.g., breast or prostate glands) in immunodeficient mice, injection of cancer cells into the left ventricle of the heart, or direct injection into bones. New transgenic mouse models of cancer have a low incidence of spontaneous bone metastasis, but cell lines derived from these tumors can be selected in vivo for increased incidence of bone metastasis. It is essential to validate and correctly interpret the lesions in models of bone metastasis to accurately correlate the data from animal models to human disease. Animal models have provided support for the “seed and soil” hypothesis of bone metastasis. However, the roles of vascular patterns in the metaphyses of long bones and rapid bone turnover in young animals in the pathogenesis of metastasis in experimental models are uncertain. Improvements in the imaging of experimental animals in vivo using fluorescent markers or light emitted from luciferase have led to increased sensitivity of detection and more accurate quantification of bone metastases. For example, imaging of human prostate carcinoma PC‐3M cells transfected with luciferase, following injection into the left