Osteoprotegerin secretion from prostate cancer is stimulated by cytokines, in vitro.
Osteoprotegerin (OPG), a member of the tumor necrosis receptor family, is produced by various tissues and inhibits osteoclast differentiation and activity. Since the metastasis of prostate cancer to bone often induces osteosclerosis, the possibility that these tumor cells secrete OPG is of interest. We have investigated whether the prostate cancer cell lines LNCaP, PC-3, and DU-145 produce and secrete OPG in vitro and if the production might be regulated by cytokines involved in remodeling of bone. OPG transcripts were detected by RT-PCR in all cell lines. OPG in culture media was analyzed by ELISA. In all three lineages, treatment with tumor necrosis factor-alpha and interleukin-1 beta dose dependently (5-5000 pM) stimulated the OPG secretion. Treatment with tumor necrosis factor-beta in increasing concentrations (1-1000 pM) stimulated OPG secretion in PC-3 but had no effect on the DU-145 and LNCaP cells. Dexamethasone (100 pM) had a small, but not significant, inhibitory effect on OPG secretion from DU-145 and LNCaP. In human non-malignant prostate cells, used as controls, there was no effect of IL-1 or TNFs on the secretion rate of OPG.
Penno
Hendrik
H
Department of Surgical Sciences, University of Uppsala, S-751 85 Uppsala, Sweden. hendrik.penno@ortopedi.uu.se
Silfverswärd
Carl-Johan
CJ
Frost
Anders
A
Brändström
Helena
H
Nilsson
Olle
O
Ljunggren
Osten
O
D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008297:Male; D053244:Osteoprotegerin; D011471:Prostatic Neoplasms; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016207:Cytokines; D006023:Glycoproteins; D007375:Interleukin-1; D008233:Lymphotoxin-alpha; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone