High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer.
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.
van den Hoogen
Christel
C
Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
van der Horst
Geertje
G
Cheung
Henry
H
Buijs
Jeroen T
JT
Lippitt
Jenny M
JM
Guzmán-Ramírez
Natalia
N
Hamdy
Freddie C
FC
Eaton
Colby L
CL
Thalmann
George N
GN
Cecchini
Marco G
MG
Pelger
Rob C M
RC
van der Pluijm
Gabri
G
D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000201:enzymology* / Q000556:secondary*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011467:Prostate / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*
D014408:Biomarkers, Tumor; D000444:Aldehyde Dehydrogenase