The influence of metastatic breast cancer on the bone microenvironment

Andrea M. Mastro, Donna M. Sosnoski, Venkatesh Krishnan, Karen M. Bussard

Research output: Chapter in Book/Report/Conference proceedingChapter


The bone is a welcoming microenvironment for metastases from many cancers including breast cancer. Cancer cells can easily enter the bone marrow cavity due to its vasculature; there they are exposed to the many growth factors and cytokines that are part of the continuous bone remodeling process. In addition, the cancer cells interact with the resident bone cells, osteoblasts and osteoclasts, to modify the microenvironment resulting in cancer cell colonization and eventually bone degradation. Osteoclasts release numerous molecules such as insulin-like growth factors (IGFs) and transforming growth factor beta (TGF-β) from the matrix. Osteoblasts undergo an inflammatory stress response and produce a set of cytokines that are osteoclastogenic. These cytokines include IL-6, IL-8 (murine homologue MIP-2), VEGF, MCP-1, MIG and LIX. Several of these molecules also are secreted by cancer cells. One notable exception is MCP-1 which is made only in small quantities. During the course of metastasis, osteoblast differentiation is suppressed and the prevalence of osteoblast apopotosis increases. Thus the bone microenvironment is modified by the interaction of cancer cells with both osteoblasts and osteoclasts. Bone loss results from hyperactive osteoclasts and hypoactive osteoblasts. This chapter summarizes the results of studies of osteoblast and breast cancer cell interactions that have been performed in cell culture, in mice and in a novel three dimensional culture bioreactor.

Original languageEnglish (US)
Title of host publicationSignaling Pathways and Molecular Mediators in Metastasis
PublisherSpringer Netherlands
Number of pages22
ISBN (Electronic)9789400725584
ISBN (Print)9400725574, 9789400725577
StatePublished - Jan 1 2012

All Science Journal Classification (ASJC) codes

  • Medicine(all)


Dive into the research topics of 'The influence of metastatic breast cancer on the bone microenvironment'. Together they form a unique fingerprint.

Cite this