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PMID: 24677373 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Molecular mechanisms of bone metastasis and associated muscle weakness.

Clinical cancer research : an official journal of the American Association for Cancer Research ·Vol. 20 ·No. 12 ·2014-06-15 ·Pages 3071-7

Waning DL, Guise TA

Abstract

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.

MeSH Terms
Animals Bone Neoplasms/complications,secondary Breast Neoplasms/pathology Female Humans Muscle Weakness/etiology,pathology Prognosis
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Waning David L
Authors' Affiliation: Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis, Indiana.
Guise Theresa A
Authors' Affiliation: Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis, Indiana tguise@iu.edu.
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Article Info
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Abbr.
Clin Cancer Res
ISSN
1557-3265
DOI
10.1158/1078-0432.CCR-13-1590
Email
tguise@iu.edu
Published
2014-06-15
Epub
2014-00-27
Pages
3071-7
Language
English
Region
United States
NLM ID
9502500
PMCID
PMC4058425
Subset
IM
Grants
NCI NIH HHS · R01 CA069158 · United States
NCI NIH HHS · U01 CA143057 · United States
NCI NIH HHS · R01CA69158 · United States
NCI NIH HHS · U01CA143057 · United States
External Links
PubMed source DOI: 10.1158/1078-0432.CCR-13-1590 PMC Full Text View journal details
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