Dormancy and growth of metastatic breast cancer cells in a bone-like microenvironment

Donna M. Sosnoski, Robert J. Norgard, Cassidy D. Grove, Shelby J. Foster, Andrea M. Mastro

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Breast cancer can reoccur, often as bone metastasis, many years if not decades after the primary tumor has been treated. The factors that stimulate dormant metastases to grow are not known, but bone metastases are often associated with skeletal trauma. We used a dormancy model of MDA-MB-231BRMS1, a metastasis-suppressed human breast cancer cell line, co-cultured with MC3T3-E1 osteoblasts in a long term, three dimensional culture system to test the hypothesis that bone remodeling cytokines could stimulate dormant cells to grow. The cancer cells attached to the matrix produced by MC3T3-E1 osteoblasts but grew slowly or not at all until the addition of bone remodeling cytokines, TNFα and IL-β. Stimulation of cell proliferation by these cytokines was suppressed with indomethacin, an inhibitor of cyclooxygenase and of prostaglandin production, or a prostaglandin E2 (PGE2) receptor antagonist. Addition of PGE2 directly to the cultures also stimulated cell proliferation. MCF-7, non-metastatic breast cancer cells, remained dormant when co-cultured with normal human osteoblast and fibroblast growth factor. Similar to the MDA-MB-231BRMS1 cells, MCF-7 proliferation increased in response to TNFα and IL-β. These findings suggest that changes in the bone microenvironment due to inflammatory cytokines associated with bone repair or excess turnover may trigger the occurrence of latent bone metastasis.

Original languageEnglish (US)
Pages (from-to)335-344
Number of pages10
JournalClinical and Experimental Metastasis
Volume32
Issue number4
DOIs
StatePublished - Apr 8 2015

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Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Osteoblasts
Cytokines
Growth
Bone Remodeling
Dinoprostone
Cell Proliferation
Prostaglandin Receptors
Prostaglandin Antagonists
Cyclooxygenase Inhibitors
Fibroblast Growth Factors
MCF-7 Cells
Prostaglandin-Endoperoxide Synthases
Indomethacin
Neoplasms
Cell Line
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sosnoski, Donna M. ; Norgard, Robert J. ; Grove, Cassidy D. ; Foster, Shelby J. ; Mastro, Andrea M. / Dormancy and growth of metastatic breast cancer cells in a bone-like microenvironment. In: Clinical and Experimental Metastasis. 2015 ; Vol. 32, No. 4. pp. 335-344.
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Dormancy and growth of metastatic breast cancer cells in a bone-like microenvironment. / Sosnoski, Donna M.; Norgard, Robert J.; Grove, Cassidy D.; Foster, Shelby J.; Mastro, Andrea M.

In: Clinical and Experimental Metastasis, Vol. 32, No. 4, 08.04.2015, p. 335-344.

Research output: Contribution to journalArticle

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