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PMID: 21355075 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Human prostate cancer harbors the stem cell properties of bone marrow mesenchymal stem cells.

Clinical cancer research : an official journal of the American Association for Cancer Research ·Vol. 17 ·No. 8 ·2011-04-15 ·Pages 2159-69

Zhau HE, He H, Wang CY, Zayzafoon M, Morrissey C, Vessella RL, Marshall FF, Chung LW, Wang R

Abstract

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. 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. 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. 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.

MeSH Terms
Adipocytes/cytology,metabolism Apoptosis/drug effects,genetics Bone Marrow Cells/metabolism Cell Differentiation/drug effects,genetics Cell Line, Transformed Cell Line, Tumor Cell Lineage Culture Media/chemistry,pharmacology Gene Expression Regulation, Neoplastic/drug effects Humans Immunohistochemistry Ion Channels/genetics,metabolism Male Mesenchymal Stem Cells/drug effects,metabolism Mitochondrial Proteins/genetics,metabolism Neoplastic Stem Cells/metabolism Osteoblasts/cytology,metabolism Prostatic Neoplasms/genetics,metabolism,pathology Reverse Transcriptase Polymerase Chain Reaction Tissue Array Analysis Uncoupling Protein 1
Chemicals
Culture Media Ion Channels Mitochondrial Proteins UCP1 protein, human Uncoupling Protein 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhau Haiyen E
Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
He Hui
Wang Christopher Y
Zayzafoon Majd
Morrissey Colm
Vessella Robert L
Marshall Fray F
Chung Leland W K
Wang Ruoxiang
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Article Info
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Abbr.
Clin Cancer Res
ISSN
1557-3265
DOI
10.1158/1078-0432.CCR-10-2523
Published
2011-04-15
Epub
2011-00-25
Pages
2159-69
Language
English
Region
United States
NLM ID
9502500
PMCID
PMC3085118
Subset
IM
Grants
NCI NIH HHS · CA97186 · United States
NCI NIH HHS · R21CA112330 · United States
NCI NIH HHS · P20 CA132388 · United States
NCI NIH HHS · P50 CA097186 · United States
NCI NIH HHS · P01 CA098912 · United States
NCI NIH HHS · P01 CA085859 · United States
NCI NIH HHS · PC040578 · United States
NCI NIH HHS · CA132388 · United States
NCI NIH HHS · R21 CA112330-02 · United States
NCI NIH HHS · R01 CA122602 · United States
NCI NIH HHS · CA98912-02 · United States
NCI NIH HHS · R21 CA112330 · United States
NCI NIH HHS · P01CA85859 · United States
External Links
PubMed source DOI: 10.1158/1078-0432.CCR-10-2523 PMC Full Text View journal details
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