Breast cancer cells induce osteoblast apoptosis: A possible contributor to bone degradation

Andrea M. Mastro, Carol V. Gay, Danny R. Welch, Henry J. Donahue, Jennifer Jewell, Robyn Mercer, Douglas DiGirolamo, Elizabeth M. Chislock, Kristin Guttridge

Research output: Contribution to journalReview article

51 Citations (Scopus)

Abstract

Breast cancer cells exhibit a predilection for metastasis to bone. There, the metastases usually bring about bone loss with accompanying pain and loss of function. One way that breast cancer cells disrupt the normal pattern of bone remodeling is by activating osteoclasts, the bone degrading cells. Nevertheless, targeting the osteoclasts does not cure the disease or result in bone repair. These observations indicate that osteoblast function also may be compromised. The objective of this study was to investigate the interaction of metastatic breast cancer cells with osteoblasts. Human metastatic breast cancer cells, MDA-MB-435 or MDA-MB-231, or their conditioned media were co-cultured with a human osteoblast line hFOB1.19. The breast cancer cells caused an increase in the prevalence of apoptotic osteoblasts. Apoptotic osteoblasts detected by the TUNEL assay or by caspase activity increased approximately two to fivefold. This increase was not seen with non-metastatic MDA-MB-468 cells. In an investigation of the mechanism, it was determined that the hFOB1.19 cells expressed fas and that fas was functional. Likewise the hFOB1.19 cells were susceptible to TNF-α, but this cytokine was not detected in the conditioned medium of the breast cancer cells. This study indicates that osteoblasts are the target of breast cancer cell-induced apoptosis, but fas/fas-ligand and TNF-α, two common initiators of cell death, are probably not involved in this aspect of the metastases/bone cell axis. There are several mechanisms that remain to be explored in order to determine how breast cancer cells bring about osteoblast apoptosis. Even though the specific initiator of apoptosis remains to be identified, the results of this study suggest that the mechanism is likely to be novel.

Original languageEnglish (US)
Pages (from-to)265-276
Number of pages12
JournalJournal of cellular biochemistry
Volume91
Issue number2
DOIs
StatePublished - Dec 1 2004

Fingerprint

Osteoblasts
Bone
Cells
Apoptosis
Breast Neoplasms
Bone and Bones
Degradation
Conditioned Culture Medium
Osteoclasts
Neoplasm Metastasis
Fas Ligand Protein
Cell death
Caspases
Assays
Repair
Bone Remodeling
Cytokines
In Situ Nick-End Labeling
Cell Death

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mastro, A. M., Gay, C. V., Welch, D. R., Donahue, H. J., Jewell, J., Mercer, R., ... Guttridge, K. (2004). Breast cancer cells induce osteoblast apoptosis: A possible contributor to bone degradation. Journal of cellular biochemistry, 91(2), 265-276. https://doi.org/10.1002/jcb.10746
Mastro, Andrea M. ; Gay, Carol V. ; Welch, Danny R. ; Donahue, Henry J. ; Jewell, Jennifer ; Mercer, Robyn ; DiGirolamo, Douglas ; Chislock, Elizabeth M. ; Guttridge, Kristin. / Breast cancer cells induce osteoblast apoptosis : A possible contributor to bone degradation. In: Journal of cellular biochemistry. 2004 ; Vol. 91, No. 2. pp. 265-276.
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Mastro, AM, Gay, CV, Welch, DR, Donahue, HJ, Jewell, J, Mercer, R, DiGirolamo, D, Chislock, EM & Guttridge, K 2004, 'Breast cancer cells induce osteoblast apoptosis: A possible contributor to bone degradation', Journal of cellular biochemistry, vol. 91, no. 2, pp. 265-276. https://doi.org/10.1002/jcb.10746

Breast cancer cells induce osteoblast apoptosis : A possible contributor to bone degradation. / Mastro, Andrea M.; Gay, Carol V.; Welch, Danny R.; Donahue, Henry J.; Jewell, Jennifer; Mercer, Robyn; DiGirolamo, Douglas; Chislock, Elizabeth M.; Guttridge, Kristin.

In: Journal of cellular biochemistry, Vol. 91, No. 2, 01.12.2004, p. 265-276.

Research output: Contribution to journalReview article

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T1 - Breast cancer cells induce osteoblast apoptosis

T2 - A possible contributor to bone degradation

AU - Mastro, Andrea M.

AU - Gay, Carol V.

AU - Welch, Danny R.

AU - Donahue, Henry J.

AU - Jewell, Jennifer

AU - Mercer, Robyn

AU - DiGirolamo, Douglas

AU - Chislock, Elizabeth M.

AU - Guttridge, Kristin

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Breast cancer cells exhibit a predilection for metastasis to bone. There, the metastases usually bring about bone loss with accompanying pain and loss of function. One way that breast cancer cells disrupt the normal pattern of bone remodeling is by activating osteoclasts, the bone degrading cells. Nevertheless, targeting the osteoclasts does not cure the disease or result in bone repair. These observations indicate that osteoblast function also may be compromised. The objective of this study was to investigate the interaction of metastatic breast cancer cells with osteoblasts. Human metastatic breast cancer cells, MDA-MB-435 or MDA-MB-231, or their conditioned media were co-cultured with a human osteoblast line hFOB1.19. The breast cancer cells caused an increase in the prevalence of apoptotic osteoblasts. Apoptotic osteoblasts detected by the TUNEL assay or by caspase activity increased approximately two to fivefold. This increase was not seen with non-metastatic MDA-MB-468 cells. In an investigation of the mechanism, it was determined that the hFOB1.19 cells expressed fas and that fas was functional. Likewise the hFOB1.19 cells were susceptible to TNF-α, but this cytokine was not detected in the conditioned medium of the breast cancer cells. This study indicates that osteoblasts are the target of breast cancer cell-induced apoptosis, but fas/fas-ligand and TNF-α, two common initiators of cell death, are probably not involved in this aspect of the metastases/bone cell axis. There are several mechanisms that remain to be explored in order to determine how breast cancer cells bring about osteoblast apoptosis. Even though the specific initiator of apoptosis remains to be identified, the results of this study suggest that the mechanism is likely to be novel.

AB - Breast cancer cells exhibit a predilection for metastasis to bone. There, the metastases usually bring about bone loss with accompanying pain and loss of function. One way that breast cancer cells disrupt the normal pattern of bone remodeling is by activating osteoclasts, the bone degrading cells. Nevertheless, targeting the osteoclasts does not cure the disease or result in bone repair. These observations indicate that osteoblast function also may be compromised. The objective of this study was to investigate the interaction of metastatic breast cancer cells with osteoblasts. Human metastatic breast cancer cells, MDA-MB-435 or MDA-MB-231, or their conditioned media were co-cultured with a human osteoblast line hFOB1.19. The breast cancer cells caused an increase in the prevalence of apoptotic osteoblasts. Apoptotic osteoblasts detected by the TUNEL assay or by caspase activity increased approximately two to fivefold. This increase was not seen with non-metastatic MDA-MB-468 cells. In an investigation of the mechanism, it was determined that the hFOB1.19 cells expressed fas and that fas was functional. Likewise the hFOB1.19 cells were susceptible to TNF-α, but this cytokine was not detected in the conditioned medium of the breast cancer cells. This study indicates that osteoblasts are the target of breast cancer cell-induced apoptosis, but fas/fas-ligand and TNF-α, two common initiators of cell death, are probably not involved in this aspect of the metastases/bone cell axis. There are several mechanisms that remain to be explored in order to determine how breast cancer cells bring about osteoblast apoptosis. Even though the specific initiator of apoptosis remains to be identified, the results of this study suggest that the mechanism is likely to be novel.

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