Molecular mechanisms of bone metastasis and associated muscle weakness.

Clin Cancer Res 2014 Jun 27;20(12):3071-7. Epub 2014 Mar 27.

Authors' Affiliation: Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis, Indiana

Bone is a preferred site for breast cancer metastasis and leads to pathologic bone loss due to increased osteoclast-induced bone resorption. The homing of tumor cells to the bone depends on the support of the bone microenvironment in which the tumor cells prime the premetastatic niche. The colonization and growth of tumor cells then depend on adaptations in the invading tumor cells to take advantage of normal physiologic responses by mimicking bone marrow cells. This concerted effort by tumor cells leads to uncoupled bone remodeling in which the balance of osteoclast-driven bone resorption and osteoblast-driven bone deposition is lost. Breast cancer bone metastases often lead to osteolytic lesions due to hyperactive bone resorption. Release of growth factors from bone matrix during resorption then feeds a "vicious cycle" of bone destruction leading to many skeletal-related events. In addition to activity in bone, some of the factors released during bone resorption are also known to be involved in skeletal muscle regeneration and contraction. In this review, we discuss the mechanisms that lead to osteolytic breast cancer bone metastases and the potential for cancer-induced bone-muscle cross-talk leading to skeletal muscle weakness.

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Source
http://dx.doi.org/10.1158/1078-0432.CCR-13-1590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058425PMC
June 2014
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