title: Expression of PGK1 by prostate cancer cells induces bone formation.
abstract: Prostate cancer (PCa) is one of the solid tumors that metastasize to the bone. Once there, the phenotype of the bone lesions is dependent upon the balance between osteoblastogenesis and osteoclastogenesis. We previously reported that overexpression of phosphoglycerate kinase 1 (PGK1) in PCa cell lines enhanced bone formation at the metastatic site in vivo. Here, the role of PGK1 in the bone formation was further explored. We show that PCa-derived PGK1 induces osteoblastic differentiation of bone marrow stromal cells. We also found that PGK1 secreted by PCa inhibits osteoclastogenesis. Finally, the expression levels of the bone-specific markers in PCa cells were higher in cells overexpressing PGK1 than controls. Together, these data suggest that PGK1 secreted by PCa regulates bone formation at the metastatic site by increasing osteoblastic activity, decreasing osteoclastic function, and expressing an osteoblastic phenotype by PCa cells.
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Jung
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shiozawa
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Wang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Pedersen
authors.forename: Clara H
authors.initials: CH
authors.lastname: Lee
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Hall
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Hogg
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000201:enzymology* / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000503:physiopathology; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D010641:Phenotype; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C528165:Pgk1 protein, mouse; D010735:Phosphoglycerate Kinase