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 lin...

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Bibliographic Details
Published in:Molecular cancer research 2009-10, Vol.7 (10), p.1595-1604
Main Authors: Jung, Younghun, Shiozawa, Yusuke, Wang, Jianhua, Wang, Jingcheng, Wang, Zhuo, Pedersen, Elisabeth A, Lee, Clara H, Hall, Christopher L, Hogg, Phillip J, Krebsbach, Paul H, Keller, Evan T, Taichman, Russell S
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Biomarkers, Tumor - metabolism
Carcinoma - enzymology
Carcinoma - physiopathology
Cell Differentiation - physiology
Cell Line
Cell Line, Tumor
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Nude
Mice, SCID
Neoplasm Metastasis - physiopathology
Osteoblastogenesis
Osteoblasts - metabolism
Osteoclastogenesis
Osteoclasts - metabolism
Osteogenesis - physiology
Phenotype
Phosphoglycerate Kinase - genetics
Phosphoglycerate Kinase - metabolism
Phosphoglycerate kinase 1 (PGK1)
Prostate cancer
Prostatic Neoplasms - enzymology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - physiopathology
Stem Cells - cytology
Stem Cells - metabolism
Stromal Cells - cytology
Stromal Cells - metabolism
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Summary: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. (Mol Cancer Res 2009;7(10):1595–604)
ISSN:1541-7786
1557-3125
DOI:10.1158/1541-7786.MCR-09-0072