PT  - JOURNAL ARTICLE
AU  - Inoue, Hitoshi
AU  - Oka, Daizo
AU  - Shiba, Masahiro
AU  - Arai, Yasuyuki
AU  - Nakayama, Masashi
AU  - Shimizu, Kiyonori
AU  - Nishimura, Kazuo
AU  - Nonomura, Norio
AU  - Okuyama, Akihiko
TI  - Prostate cancer mediates osteoclastogenesis through two different pathways
DP  - 2005 May 01
TA  - Cancer Research
PG  - 686--687
VI  - 65
IP  - 9 Supplement
4099  - http://cancerres.aacrjournals.org/content/65/9_Supplement/686.4.short
4100  - http://cancerres.aacrjournals.org/content/65/9_Supplement/686.4.full
SO  - Cancer Res2005 May 01; 65
AB  - Proc Amer Assoc Cancer Res, Volume 46, 2005 2924 Genrally, prostatic cancer shows osteoblastic metastases, whereas the lesion also causes osteolysis. The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Using a reverse transcription-polymerase chain reaction approach, we investigated the effects of crude conditioned medium (CM) obtained from prostate cancer cell lines on mRNA level of receptor activator of NF-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG) in mouse osteoblastic cell line, MC3T3-E1. Then we cocultured MC3T3-E1 with prostate cancer cell lines and evaluated mRNA level of RANKL and OPG in MC3T3-E1. Next, to investigate the effects on osteoclast precursor generated from mouse bone marrow treated with RANKL and MCSF, we cultured osteoclast precursor with crude CM obtained from prostate cancer cell lines in the presence or absence of RANKL or OPG. The number of multinucleated osteoclasts was evaluated by TRAP staining. Crude CM from all four prostate cancer cell lines enhanced expression of the mRNA for RANKL in MC3T3-E1; however, CM had no effect on expression of 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. 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.