title: Human prostate cancer harbors the stem cell properties of bone marrow mesenchymal stem cells.
abstract: OBJECTIVE
  Prostate tumor cells frequently show the features of osteoblasts, which are differentiated from bone marrow mesenchymal stem cells. We examined human prostate cancer cell lines and clinical prostate cancer specimens for additional bone marrow mesenchymal stem cell properties.
  
  
  METHODS
  Prostate cancer cell lines were induced for osteoblastogenic and adipogenic differentiation, detected by standard staining methods and confirmed by lineage-specific marker expression. Abnormal expression of the markers was then assessed in clinical prostate cancer specimens.
  
  
  RESULTS
  After osteoblastogenic induction, cells of the LNCaP lineage, PC-3 lineage, and DU145 displayed osteoblastic features. Upon adipogenic induction, PC-3 lineage and DU145 cells differentiated into adipocyte-like cells. The adipocyte-like cancer cells expressed brown adipocyte-specific markers, suggesting differentiation along the brown adipocyte lineage. The adipogenic differentiation was accompanied by growth inhibition, and most of the adipocyte-like cancer cells were committed to apoptotic death. During cyclic treatments with adipogenic differentiation medium and then with control medium, the cancer cells could commit to repeated adipogenic differentiation and retrodifferentiation. In clinical prostate cancer specimens, the expression of uncoupling protein 1 (UCP1), a brown fat-specific marker, was enhanced with the level of expression correlated to disease progression from primary to bone metastatic cancers.
  
  
  CONCLUSIONS
  This study thus revealed that prostate cancer cells harbor the stem cell properties of bone marrow mesenchymal stem cells. The abnormally expressed adipogenic UCP1 protein may serve as a unique marker, while adipogenic induction can be explored as a differentiation therapy for prostate cancer progression and bone metastasis.
authors.affiliation: Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Wang
authors.forename: Majd
authors.initials: M
authors.lastname: Zayzafoon
authors.forename: Colm
authors.initials: C
authors.lastname: Morrissey
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Fray F
authors.initials: FF
authors.lastname: Marshall
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.forename: Ruoxiang
authors.initials: R
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D019070:Cell Lineage; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D000071256:Uncoupling Protein 1
chemical_list: D003470:Culture Media; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1