Emerging and Established Models of Bone Metastasis

Abstract

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. Bone is the primary site of metastasis for several cancers—breast and prostate cancers in particular. Efforts to treat bone metastases have been stymied by a lack of models to study the progression, cellular players, and signaling pathways driving bone metastasis. In this review, we examine newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic, and in silico computational bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cells enter and then escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.

CD117/c-kit Defines a Prostate CSC-Like Subpopulation Driving Progression and TKI Resistance

“…Further research is required to verify that CD117 expressing cells represent CSCs in patients and that these cells initiate bone metastases, which would require the development of new bone metastases models. [86] In summary, we demonstrate that the CD117 subpopulation of LNCaP-C4-2 prostate cancer cells represents CSCs driving progression, migration, and TKI resistance. Harris 22…”

Novel and Conventional Preclinical Models to Investigate Bone Metastasis

“…In systemic models, the cancer cells (seeds) are inoculated to the systemic circulation and let to home to their preferred sites (soils). These models are often described to be the real bone metastasis models as they include the early steps in the formation of metastases, including the survival in circulation, extravasation, dissemination to the bone, and finally dormancy and/or growth of bone metastases [1,2,4]. Additionally, disseminated and dormant tumor models have been characterized, bringing new possibilities to study these rare events [1, 2, 3•].…”

“…Bone metastases are a major cause of morbidity and mortality in cancer patients [1][2][3]. Seventy to eighty percent of advanced breast and prostate cancer patients develop bone metastases, and metastases are also very common in lung, kidney, and thyroid cancers and in melanoma [2, 3•, 4].…”

“…Thus, bone metastases are a major influencer in the natural history of these cancers. Bone metastases cause severe pain and increase the risk of fractures leading to decreased quality of life [2,4]. The median survival time after diagnosis of bone metastases is only 2-3 years [2] and therefore, there is a great need to develop cancer therapies targeting bone metastatic disease.…”

“…Different models that can be used to study bone metastasis are extensively described by Jinnah and colleagues [2]. Additionally, Simmons and colleagues explain in detail the models both by cell type and by inoculation route, as well as other approaches like inducible models [3•].…”