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Metastatic progression of advanced prostate cancer is a major clinical problem. Identifying the cell(s) of origin in prostate cancer and its distant metastases may permit the development of more effective treatment and preventive therapies. In this study, aldehyde dehydrogenase (ALDH) activity was used as a basis to isolate and compare subpopulations of primary human prostate cancer cells and cell lines. ALDH-high prostate cancer cells displayed strongly elevated clonogenicity and migratory behavior in vitro. More strikingly, ALDH-high cells readily formed distant metastases with strongly enhanced tumor progression at both orthotopic and metastatic sites in preclinical models. Several ALDH isoforms were expressed in human prostate cancer cells and clinical specimens of primary prostate tumors with matched bone metastases. Our findings suggest that ALDH-based viable cell sorting can be used to identify and characterize tumor-initiating and, more importantly perhaps, metastasis-initiating cells in human prostate cancer.

Original publication

DOI

10.1158/0008-5472.CAN-09-3806

Type

Journal article

Journal

Cancer Res

Publication Date

15/06/2010

Volume

70

Pages

5163 - 5173

Keywords

Aldehyde Dehydrogenase, Animals, Biomarkers, Tumor, Blotting, Western, Bone Neoplasms, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic, Disease Progression, Flow Cytometry, Humans, Immunoenzyme Techniques, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Prostate, Prostatic Neoplasms