Skip to main content

Advertisement

Log in

Metastatic breast cancer cells suppress osteoblast adhesion and differentiation

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BSP:

bone sialoprotein

IRM:

interference reflection microscopy

OCN:

osteocalcin

OSN:

osteonectin

TGFβ :

transforming growth factor β

References

  • SH Landis T Murray S Bolden et al. (1999) ArticleTitleCancer statistics Clinical & Experimental Metastasis 49 8–31

    Google Scholar 

  • CS Galasko (1982) ArticleTitleMechanisms of lytic and blastic metastatic disease of bone Clinical & Experimental Metastasis 169 20–7

    Google Scholar 

  • TA Guise GR Mundy (1998) ArticleTitleCancer and bone Clinical & Experimental Metastasis 19 18–54

    Google Scholar 

  • AF Stewart A Vignery A Silverglate et al. (1982) ArticleTitleQuantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity Clinical & Experimental Metastasis 55 219–27

    Google Scholar 

  • SC Kukreja TJ Rosol DH Shevrin et al. (1988) ArticleTitleQuantitative bone histomorphometry in nude mice bearing a human squamous cell lung cancer Clinical & Experimental Metastasis 3 341–6

    Google Scholar 

  • PD Delmas B Demiaux L Malaval et al. (1986) ArticleTitleSerum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry Clinical & Experimental Metastasis 77 985–91

    Google Scholar 

  • T Taube I Elomaa C Blomqvist et al. (1994) ArticleTitleHistomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer Clinical & Experimental Metastasis 15 161–6

    Google Scholar 

  • AM Mastro CV Gay DR Welch et al. (2004) ArticleTitleBreast cancer cells induce osteoblast apoptosis: A possible contributor to bone degradation Clinical & Experimental Metastasis 91 265–76

    Google Scholar 

  • O Fromigue N Kheddoumi A Lomri et al. (2001) ArticleTitleBreast cancer cells release factors that induced apoptosis in human bone marrow stromal cells Clinical & Experimental Metastasis 16 1600–10

    Google Scholar 

  • M Lacroix B Siwek JJ Body (1996) ArticleTitleEffects of secretory products of breast cancer cells on osteoblast-like cells Clinical & Experimental Metastasis 38 209–16

    Google Scholar 

  • B Siwek M Lacroix C De Pollak et al. (1997) ArticleTitleSecretory products of breast cancer cells specifically affect human osteoblastic cells: partial characterization of active factors Clinical & Experimental Metastasis 12 552–60

    Google Scholar 

  • P Bunyaratavej TG Hullinger MJ Somerman (2000) ArticleTitleBone morphogenetic proteins secreted by breast cancer cells upregulate bone sialoprotein expression in preosteoblast cells Clinical & Experimental Metastasis 260 324–33

    Google Scholar 

  • TG Hullinger RS Taichman DA Linseman et al. (2000) ArticleTitleSecretory products from PC-3 and MCF-7 tumor cell lines upregulate osteopontin in MC3T3-E1 cells Clinical & Experimental Metastasis 78 607–16

    Google Scholar 

  • LD Quarles DA Yohay LW Lever et al. (1992) ArticleTitleDistinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development Clinical & Experimental Metastasis 7 683–92

    Google Scholar 

  • R Cailleau R Young M Olive et al. (1974) ArticleTitleBreast tumor cell lines from pleural effusions Clinical & Experimental Metastasis 53 661–74

    Google Scholar 

  • T Yoneda A Sasaki GR Mundy (1994) ArticleTitleOsteolytic bone metastasis in breast cancer Clinical & Experimental Metastasis 32 73–84

    Google Scholar 

  • JA Hildebrand D Rugar RN Johnston et al. (1981) ArticleTitleAcoustic microscopy of living cells Clinical & Experimental Metastasis 78 1656–60

    Google Scholar 

  • JB Lian GS Stein (1992) ArticleTitleConcepts of osteoblast growth and differentiation: basis for modulation of bone cell development and tissue formation Clinical & Experimental Metastasis 3 269–305

    Google Scholar 

  • L Pederson B Winding NT Foged et al. (1999) ArticleTitleIdentification of breast cancer cell line-derived paracrine factors that stimulate osteoclast activity Clinical & Experimental Metastasis 59 5849–55

    Google Scholar 

  • Bonewald LF. Transforming growth factor-β. In Principles of Bone Biology, 2nd ed, Vol. 2. San Diego: Academic Press 2002; 903–18.

  • S Spinella-Jaegle S Roman-Roman C Faucheu et al. (2001) ArticleTitleOpposite effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on osteoblast differentiation Clinical & Experimental Metastasis 29 323–30

    Google Scholar 

  • CH Damsky (1999) ArticleTitleExtracellular matrix-integrin interactions in osteoblast function and tissue remodeling Clinical & Experimental Metastasis 25 95–6

    Google Scholar 

  • JH Bennett S Moffatt M Horton (2001) ArticleTitleCell adhesion molecules in human osteoblasts: structure and function Clinical & Experimental Metastasis 16 603–11

    Google Scholar 

  • G Xiao D Wang MD Benson et al. (1998) ArticleTitleRole of the alpha2-integrin in osteoblast-specific gene expression and activation of the Osf2 transcription factor Clinical & Experimental Metastasis 273 32988–94

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrea M. Mastro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mercer, R.R., Miyasaka, C. & Mastro, A.M. Metastatic breast cancer cells suppress osteoblast adhesion and differentiation. Clin Exp Metastasis 21, 427–435 (2004). https://doi.org/10.1007/s10585-004-1867-6

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-004-1867-6

Keywords

Navigation