title: Characterization of osteoblastic and osteolytic proteins in prostate cancer bone metastases.
abstract: BACKGROUND
  Approximately 90% of patients who die of Prostate Cancer (PCa) have bone metastases, which promote a spectrum of osteoblastic, osteolytic or mixed bone responses. Numerous secreted proteins have been reported to promote osteoblastic or osteolytic bone responses. We determined whether previously identified and/or novel proteins were associated with the osteoblastic or osteolytic response in clinical specimens of PCa bone metastases.
  
  
  METHODS
  Gene expression was analyzed on 14 PCa metastases from 11 patients by microarray profiling and qRT-PCR, and protein expression was analyzed on 33 PCa metastases from 30 patients by immunohistochemistry on highly osteoblastic and highly osteolytic bone specimens.
  
  
  RESULTS
  Transcript and protein levels of BMP-2, BMP-7, DKK-1, ET-1, and Sclerostin were not significantly different between osteoblastic and osteolytic metastases. However, levels of OPG, PGK1, and Substance P proteins were increased in osteoblastic samples. In addition, Emu1, MMP-12, and sFRP-1 were proteins identified with a novel role of being associated with either the osteoblastic or osteolytic bone response.
  
  
  CONCLUSIONS
  This is the first detailed analysis of bone remodeling proteins in human specimens of PCa bone metastases. Three proteins not previously shown to be involved may have a role in the PCa bone response. Furthermore, our data suggests that the relative expression of numerous, rather than a single, bone remodeling proteins determine the bone response in PCa bone metastases.
authors: Department of Urology, University of Washington, Seattle, Washington 98195, USA.
authors: Sandy R
authors: SR
authors: Larson
authors: Xiaotun
authors: X
authors: Zhang
authors: Ruth
authors: R
authors: Dumpit
authors: Ilsa
authors: I
authors: Coleman
authors: Bryce
authors: B
authors: Lakely
authors: Martine
authors: M
authors: Roudier
authors: Celestia S
authors: CS
authors: Higano
authors: Lawrence D
authors: LD
authors: True
authors: Paul H
authors: PH
authors: Lange
authors: Bruce
authors: B
authors: Montgomery
authors: Eva
authors: E
authors: Corey
authors: Peter S
authors: PS
authors: Nelson
authors: Robert L
authors: RL
authors: Vessella
authors: Colm
authors: C
authors: Morrissey
mesh_terms: D000368:Aged; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D016723:Bone Remodeling / Q000235:genetics; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010014:Osteolysis; D010735:Phosphoglycerate Kinase / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013373:Substance P / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D013373:Substance P; C577282:PGK1 protein, human; D010735:Phosphoglycerate Kinase