Breast cancer cells induce osteoblast apoptosis: a possible contributor to bone degradation.
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-alpha, 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-alpha, 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.
Mastro
Andrea M
AM
Department of Biochemistry and Molecular Cell Biology, The Pennsylvania State University, University Park, Pennsylvania, USA. A36@PSU.EDU
Gay
Carol V
CV
Welch
Danny R
DR
Donahue
Henry J
HJ
Jewell
Jennifer
J
Mercer
Robyn
R
DiGirolamo
Douglas
D
Chislock
Elizabeth M
EM
Guttridge
Kristin
K
D017209:Apoptosis; D001842:Bone and Bones / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods; D017077:Culture Media, Conditioned; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor