Expression of PGK1 by prostate cancer cells induces bone formation.
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.
Jung
Younghun
Y
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
Shiozawa
Yusuke
Y
Wang
Jianhua
J
Wang
Jingcheng
J
Wang
Zhuo
Z
Pedersen
Elisabeth A
EA
Lee
Clara H
CH
Hall
Christopher L
CL
Hogg
Phillip J
PJ
Krebsbach
Paul H
PH
Keller
Evan T
ET
Taichman
Russell S
RS
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
D014408:Biomarkers, Tumor; C528165:Pgk1 protein, mouse; D010735:Phosphoglycerate Kinase