Molecular mechanisms of bone metastasis and associated muscle weakness

David L. Waning, Theresa Guise

Research output: Contribution to journalArticle

48 Citations (Scopus)

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 osteoblastdriven 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.

Original languageEnglish
Pages (from-to)3071-3077
Number of pages7
JournalClinical Cancer Research
Volume20
Issue number12
DOIs
StatePublished - Jun 15 2014

Fingerprint

Muscle Weakness
Neoplasm Metastasis
Bone and Bones
Bone Resorption
Bone Neoplasms
Osteoclasts
Neoplasms
Breast Neoplasms
Skeletal Muscle
Bone Matrix
Bone Remodeling
Muscle Contraction
Bone Marrow Cells
Regeneration
Intercellular Signaling Peptides and Proteins
Muscles
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular mechanisms of bone metastasis and associated muscle weakness. / Waning, David L.; Guise, Theresa.

In: Clinical Cancer Research, Vol. 20, No. 12, 15.06.2014, p. 3071-3077.

Research output: Contribution to journalArticle

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