Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2

Nagalakshmi Nadiminty, Wei Lou, Soo Ok Lee, Farideh Mehraein-Ghomi, Jason S. Kirk, Jeffrey M. Conroy, Haitao Zhang, Allen C Gao

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Purpose: The high prevalence of osteoblastic bone metastases in prostate cancer involves the production of osteoblast-stimulating factors by prostate cancer cells. Prostate-specific antigen (PSA) is a serine protease uniquely produced by prostate cancer cells and is an important serologic marker for prostate cancer. In this study, we examined the role of PSA in the induction of osteoblast differentiation. Experimental Design: Human cDNA containing a coding region for PSA was transfected into human osteosarcoma SaOS-2 cells. SaOS-2 cells were also treated with exogenously added PSA. We evaluated changes in global gene expression using cDNA arrays and Northern blot analysis resulting from expression of PSA in human osteosarcoma SaOS-2 cells. Results: SaOS-2 cells expressing PSA had markedly up-regulated expression of genes associated with osteoblast differentiation including runx-2 and osteocalcin compared with the controls. Consistent with these results, the stable clones expressing PSA showed increased mineralization and increased activity of alkaline phosphatase in vitro compared with controls, suggesting that these cells undergo osteoblast differentiation. We also found that osteoprotegerin expression was down-regulated and that the receptor activator of NF-κB ligand expression was up-regulated in cells expressing PSA compared with controls. Conclusions: Modulation of the expression of osteogenic genes and alteration of the balance between osteoprotegerin - receptor activator of NF-κB ligand by PSA suggests that PSA produced by metastatic prostate cancer cells may participate in bone remodeling in favor of the development of osteoblastic metastases in the heterogeneous mixture of osteolytic and osteoblastic lesions. These findings provide a molecular basis for understanding the high prevalence of osteoblastic bone metastases in prostate cancer.

Original languageEnglish (US)
Pages (from-to)1420-1430
Number of pages11
JournalClinical Cancer Research
Volume12
Issue number5
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

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Bone Remodeling
Osteosarcoma
Prostate-Specific Antigen
Osteoblasts
Cell Line
Prostatic Neoplasms
Genes
Osteoprotegerin
Neoplasm Metastasis
Gene Expression
Ligands
Bone and Bones
Osteocalcin
Serine Proteases
Oligonucleotide Array Sequence Analysis
Northern Blotting
Alkaline Phosphatase
Research Design
Complementary DNA
Clone Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2. / Nadiminty, Nagalakshmi; Lou, Wei; Lee, Soo Ok; Mehraein-Ghomi, Farideh; Kirk, Jason S.; Conroy, Jeffrey M.; Zhang, Haitao; Gao, Allen C.

In: Clinical Cancer Research, Vol. 12, No. 5, 01.03.2006, p. 1420-1430.

Research output: Contribution to journalArticle

Nadiminty, Nagalakshmi ; Lou, Wei ; Lee, Soo Ok ; Mehraein-Ghomi, Farideh ; Kirk, Jason S. ; Conroy, Jeffrey M. ; Zhang, Haitao ; Gao, Allen C. / Prostate-specific antigen modulates genes involved in bone remodeling and induces osteoblast differentiation of human osteosarcoma cell line SaOS-2. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 5. pp. 1420-1430.
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