Emerging and Established Models of Bone Metastasis.

Alexander Jinnah,Bethany Kerr,Chukwuweike Gwam,Benjamin Zacks

doi:10.3390/cancers10060176

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.

Highlights

Bone is a common site of metastatic cancer, with an estimated 280,000 adults in the UnitedStates suffering from metastatic bone disease [1]
Metastatic bone disease poses a significant burden on the healthcare economy
Tumors shed approximately 3.2 × 106 cells/g tissue per day; only 0.01% of these cells survive the rigors of the systemic circulation and develop into metastases [12,13]

Summary

Introduction

Bone is a common site of metastatic cancer, with an estimated 280,000 adults in the UnitedStates suffering from metastatic bone disease [1]. Lung, thyroid, kidney, and most adenocarcinoma primary tumors are reported to metastasize to bone, albeit less frequently [2,4]. These bone lesions cause serious skeletal complications, including spinal cord or nerve root compression, hypercalcemia of malignancy, pathologic fractures, and debilitating bone pain [1]. The median survival after a diagnosis of overt skeletal metastases is approximately 2–3 years [5,6] These aforementioned facts illustrate the clinical importance of preventing or curing bone metastasis. With the current emphasis on decreasing healthcare expenditure, a significant step towards a curative or preventive treatment for bone metastases would undoubtedly address a clinical and economic problem in one fell swoop

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