| Expression of Osteoprotegerin and RANK Ligand
in Prostate Cancer Bone Metastasis
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| 전립선암의 골 전이 시 Osteoprotegerin 및 RANK Ligand의 발현 |
| 박혜림,김정화1,장기택,장재석2 |
| 한림대학교 의과대학 병리학교실, 아산생명과학연구소1,
울산대학교 의과대학 서울중앙병원 정형외과2
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| Abstract |
Purpose
Prostate cancer frequently metastasizes to the bone. Although prostate cancer metastases have an overall osteoblastic phenotype, histological examination reveals that they have an osteolytic component. Several factors may contribute to prostate cancer induced osteoclastogenesis. The interactions of the recently discovered proteins OPG and RANKL are crucial in osteoclastogenesis and therefore in bone homeostasis. To explore the role of OPG and RANKL in prostate cancer skeletal metastasis, we determined the ability of PC-3 cells to induce osteoclastogenesis in vitro.
Materias and Methods: To determine if this effect was mediated by soluble factors, we used conditioned media from co-cultured cells. PC-3 cells were directly co-cultured with ST2, MC3T3-E1, or primary mouse calvarial cells. Osteoclast-like cells and TRAP activity were then quantitated in murine bone marrow culture. We examined these cell lines for the expression of OPG and RANKL mRNA by RT-PCR.
Results
Co-culture of PC-3 cells with stromal or osteoblastic cells induced an increase in osteoclast number and TRAP activity compared to controls. PC-3 cells alone 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.
Conclusion
These experiments demonstrate that interactions between prostate cancer and stromal or osteoblastic cells induce osteoclastogenesis in vitro through RANKL. Prostate cancer-expressed OPG and RANKL are instrumental in the development of early osteolytic lesions observed in prostate cancer bone metastasis.
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| Key Words:
Prostate cancer, Bone metastasis, Osteoclastogenesis, OPG, RANKL |
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