Expression of Osteoprotegerin and RANK Ligand in Breast Cancer Bone Metastasis.
10.3346/jkms.2003.18.4.541
- Author:
Hye Rim PARK
1
;
Soo Kee MIN
;
Hyun Deuk CHO
;
Duck Hwan KIM
;
Hyung Sik SHIN
;
Young Euy PARK
Author Information
1. Department of Pathology, College of Medicine, Hallym University, Chuncheon, Korea. hyerim@chol.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Breast Neoplasms;
Bone and Bones;
Neoplasm Metastasis;
Osteoclasts
- MeSH:
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
- From:Journal of Korean Medical Science
2003;18(4):541-546
- CountryRepublic of Korea
- Language:English
-
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.
