Cancer research (Chicago, Ill.), 2005-03, Vol.65 (5), p.1710-1718
2005
Details
- Autor(en) / Beteiligte
- Titel
- Osteoprotegerin in prostate cancer bone metastasis
- Ist Teil von
- Cancer research (Chicago, Ill.), 2005-03, Vol.65 (5), p.1710-1718
- Ort / Verlag
- Philadelphia, PA: American Association for Cancer Research
- Erscheinungsjahr
- 2005
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Osteoprotegerin (OPG), a critical regulator of osteoclastogenesis, is expressed by prostate cancer cells, and OPG levels are increased in patients with prostate cancer bone metastases. The objective of this study was to investigate the effects of OPG overexpression on prostate cancer cells and prostate cancer/bone cell interactions in vitro and in vivo. OPG-transfected C4-2 cells expressed 8.0 ng OPG per mL per 10(6) cells, whereas no OPG was detected in the media of C4-2 cells transfected with a control plasmid. OPG overexpressed by C4-2 cells protected these cells from tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis and decreased osteoclast formation. Subcutaneous OPG-C4-2 and pcDNA-C4-2 tumors exhibited similar growth and take-rate characteristics. However, when grown in bone, tumor volume was decreased in OPG-C4-2 versus pcDNA-C4-2 (P=0.0017). OPG expressed by C4-2 cells caused increases in bone mineral density (P=0.0074) and percentage of trabecular bone volume (P=0.007), and decreases in numbers of osteoblasts and osteoclasts when compared with intratibial pcDNA-C4-2 tumors (P=0.003 and P=0.019, respectively). In summary, our data show that increased expression of OPG in C4-2 cells does not directly affect proliferation of prostate cancer cells but indirectly decreases growth of C4-2 tumors in the bone environment. Our data also show that OPG expressed by C4-2 cells inhibits bone lysis associated with C4-2 bone metastasis, which results in net increases in bone volume. We therefore hypothesize that OPG expressed in prostate cancer patient bone metastases may be at least partially responsible for the osteoblastic character of most prostate cancer bone lesions.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.CAN-04-2033Titel-ID: cdi_proquest_miscellaneous_67498940
- Format
- –
- Schlagworte
- Animals, Antineoplastic agents, Apoptosis - drug effects, Apoptosis Regulatory Proteins, Biological and medical sciences, Bone Neoplasms - metabolism, Bone Neoplasms - secondary, Culture Media, Conditioned, Diseases of the osteoarticular system, Glycoproteins - genetics, Glycoproteins - metabolism, Humans, Male, Medical sciences, Membrane Glycoproteins - pharmacology, Mice, Mice, SCID, Nephrology. Urinary tract diseases, Osteoblasts - metabolism, Osteoblasts - pathology, Osteoclasts - metabolism, Osteoclasts - pathology, Osteolysis - metabolism, Osteolysis - pathology, Osteoprotegerin, Pharmacology. Drug treatments, Prostatic Neoplasms - metabolism, Prostatic Neoplasms - pathology, Receptors, Cytoplasmic and Nuclear - genetics, Receptors, Cytoplasmic and Nuclear - metabolism, Receptors, Tumor Necrosis Factor, RNA, Messenger - metabolism, Survival Rate, TNF-Related Apoptosis-Inducing Ligand, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha - pharmacology, Tumors of striated muscle and skeleton, Tumors of the urinary system, Up-Regulation, Urinary tract. Prostate gland