J Korean Med Sci.  2003 Aug;18(4):541-546. 10.3346/jkms.2003.18.4.541.

Expression of Osteoprotegerin and RANK Ligand in Breast Cancer Bone Metastasis

• Park HR
• Min SK
• Cho HD
• Kim DH
• Shin HS
• Park YE

• KMID: 648906
• DOI: http://doi.org/10.3346/jkms.2003.18.4.541

Abstract

Bone destruction is primarily mediated by osteoclastic bone resorption, and cancer cells stimulate the formation and activation of osteoclasts next to metastatic foci. Accumulating evidences indicate that receptor activator of NF-kB ligand (RANKL) is the ultimate extracellular mediator that stimulates osteoclast differentiation into mature osteoclasts. In contrast, osteoprotegerin (OPG) inhibits osteoclast development. In order to elucidate a mechanism for cancer-induced osteoclastogenesis, cells from a human breast cancer line, MDA-MB-231, were directly co-cultured with ST2, MC3T3-E1, or with primary mouse calvarial cells. Osteoclast-like cells and tartarate resistant acid phosphatase (TRAP) activities were then quantitated. We examined these cell lines and samples from breast cancer by RT-PCR for the expressions of OPG and RANKL mRNA. Compared to controls, co-culture of MDA-MB-231 cells with stromal or osteoblastic cells induced an increase in number of osteoclasts and TRAP activities. MDA-MB-231 cells alone or breast cancer samples did not express RANKL mRNA. However, co-culture of these cancer cells with stromal or osteoblastic cells induced RANKL mRNA expression and decreased OPG mRNA expression. These experiments demonstrate that direct interactions between breast cancer and stromal or osteoblastic cells induce osteoclastogenesis in vitro through modulating RANKL expression.

Keyword

Breast Neoplasms; Bone and Bones; Neoplasm Metastasis; Osteoclasts

MeSH Terms

3T3 Cells
Acid Phosphatase/metabolism
Animals
Bone Neoplasms/*metabolism/*secondary
Breast Neoplasms/*pathology
Carrier Proteins/*biosynthesis
Cell Differentiation
Cell Line, Tumor
Cells, Cultured
Coculture
Culture Media, Conditioned/pharmacology
Glycoproteins/*biosynthesis
Human
Isoenzymes/metabolism
Male
Membrane Glycoproteins/*biosynthesis
Mice
Mice, Inbred C57BL
Neoplasm Metastasis
Osteoblasts/metabolism
Osteoclasts/metabolism
Protein Binding
RNA, Messenger/metabolism
Receptors, Cytoplasmic and Nuclear/*biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Time Factors