Clinical & Experimental Metastasis

, Volume 21, Issue 5, pp 427–435 | Cite as

Metastatic breast cancer cells suppress osteoblast adhesion and differentiation

  • Robyn R. Mercer
  • Chiaki Miyasaka
  • Andrea M. Mastro
Article

Abstract

Bone is a primary target for colonization of metastatic breast cancer cells. Once present, the breast cancer cells activate osteoclasts, thereby stimulating bone loss. Bone degradation is accompanied by pain and increased susceptibility to fractures. However, targeted inhibition of osteoclasts does not completely prevent lesion progression, nor does it heal the lesions. This suggests that breast cancer cells may also affect osteoblasts, cells that build bone. The focus of this study was to determine the ability of breast cancer cells to alter osteoblast function. MC3T3-E1 osteoblasts were cultured with conditioned medium from MDA-MB-231 breast cancer cells and subsequently assayed for changes in differentiation. Osteoblast differentiation was monitored by expression of osteocalcin, bone sialoprotein and alkaline phosphatase, and by mineralization. Osteoblasts cultured with MDA-MB-231 conditioned medium did not express these mature bone proteins, nor did they mineralize a matrix. Inhibition of osteoblast differentiation was found to be due to transforming growth factor β present in MDA-MB-231 conditioned medium. Interestingly, breast cancer conditioned medium also altered cell adhesion. When osteoblasts were assayed for adhesion properties using interference reflection microscopy and scanning acoustic microscopy, there was a reduction in focal adhesion plaques and sites of detachment were clearly visible. F-actin was disassembled and punctate in osteoblasts cultured with MDA-MB-231 conditioned medium rather than organized in long stress fibers. Taken together, these observations suggest that metastatic breast cancer cells alter osteoblast adhesion and prevent differentiation. These affects could account for the continued loss of bone after osteoclast inhibition in patients with bone-metastatic breast cancer.

Keywords

adhesion bone breast cancer differentiation metastasis osteoblasts 

Abbreviations

BSP

bone sialoprotein

IRM

interference reflection microscopy

OCN

osteocalcin

OSN

osteonectin

TGFβ

transforming growth factor β

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Robyn R. Mercer
    • 1
    • 3
  • Chiaki Miyasaka
    • 2
  • Andrea M. Mastro
    • 1
    • 3
    • 4
  1. 1.Department of Biochemistry and Molecular Biologythe Pennsylvania State UniversityUniversity ParkUSA
  2. 2.Department of Engineering Sciences and Mechanicsthe Pennsylvania State UniversityUniversity ParkUSA
  3. 3.National Foundation for Cancer Research, Center for Metastasis ResearchUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Andrea MastroUniversity ParkUSA

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