Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.
Keywordscancer; mammary; prostate; squamous cell carcinoma; dog; cat; parathyroid hormone; related protein; osteoblastic Cancer is the second leading cause of death in the United States, behind only heart disease. Death in patients with cancer is often due to metastasis, and one of the most common sites is bone. 109 Skeletal metastases are frequent in patients with breast, prostate, and lung cancer but also occur in other tumors such as myeloma, thyroid and renal cancer, lymphoma, Ewing sarcoma, and infrequently in other cancers. 110,146 Bone metastases can result in osteolytic (bone-resorbing) or osteoblastic (bone-forming) metastases that can cause pain, pathologic fractures, and mortality. 108,163 The general pathogenesis of bone metastasis involves proliferation of the primary neoplasm, local tissue invasion, intravasation into blood vessels, extravasation into the bone marrow, a Reprints and permission: sagepub.com/journalsPermissions.nav Corresponding Author: T. J. Rosol, Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Rd., Columbus, OH 43210, USA. rosol.1@osu.edu.
Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
HHS Public AccessAuthor manuscript Vet Pathol. Author manuscript; available in PMC 2015 September 01.
Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript variable time of tumor cell dormancy, proliferation in bone, and modification of the bone microenvironment. 30 The current hypothesis for preferential localization of cancer cells in bone is the "seed and soil" hypothesis of Paget, 95 which states that neoplastic cells (seeds) grow or proliferate only in a suitable soil, such as the bone marrow. This hypothesis has remained intact for over 100 years; however, now there is a deeper appreciation for the important role that the bone marrow microenvironment plays in metastasis. The metastatic tumor...