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.
Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
Christel
C
van den Hoogen
Geertje
G
van der Horst
Henry
H
Cheung
Jeroen T
JT
Buijs
Jenny M
JM
Lippitt
Natalia
N
Guzmán-Ramírez
Freddie C
FC
Hamdy
Colby L
CL
Eaton
George N
GN
Thalmann
Marco G
MG
Cecchini
Rob C M
RC
Pelger
Gabri
G
van der Pluijm
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