Prostate cancer mediates osteoclastogenesis through two different pathways.
The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Crude conditioned medium (CM) from all four prostate cancer cell lines enhanced expression of the mRNA for receptor activator of NF-kappaB ligand (RANKL) in a mouse osteoblast cell line, MC3T3-E1; however, CM had no effect on expression of osteoprotegerin (OPG) mRNA. Coculture of MC3T3-E1 with prostate cancer cells yielded similar results. The number of mature osteoclasts induced by soluble RANKL increased significantly when osteoclast precursor cells were cultured with CM from LNCaP and DU145 cells. CM from LNCaP and DU145 cells also induced maturation from precursor in the absence of soluble RANKL, and this effect was not blocked by OPG. Addition of CM from DU145 cells increased expression of MMP-9 mRNA by osteoclast precursors. Our findings indicate that prostate cancer mediates osteoclastogenesis through induction of RANKL expression by osteoblasts and through direct actions on osteoclast precursors mediated by some factors other than RANKL.
Inoue
Hitoshi
H
Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nishimura
Kazuo
K
Oka
Daizo
D
Nakai
Yasutomo
Y
Shiba
Masahiro
M
Tokizane
Takashi
T
Arai
Yasuyuki
Y
Nakayama
Masashi
M
Shimizu
Kiyonori
K
Takaha
Natsuki
N
Nonomura
Norio
N
Okuyama
Akihiko
A
D001859:Bone Neoplasms / Q000191:economics*; D002352:Carrier Proteins / Q000235:genetics*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020780:Matrix Metalloproteinase 9