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... Show moreMetastatic 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. Cancer Res; 70(12); 5163-73. (C) 2010 AACR. Show less
Eaton, C.L.; Colombel, M.; Pluijm, G. van der; Cecchini, M.; Wetterwald, A.; Lippitt, J.; ... ; Thalman, G. 2010
BACKGROUND. Tumour cells with a stem cell-like phenotype have recently been identified in prostate tumors and it has been suggested that this population may be responsible for the diversity of cell... Show moreBACKGROUND. Tumour cells with a stem cell-like phenotype have recently been identified in prostate tumors and it has been suggested that this population may be responsible for the diversity of cell types within tumors and also for the initiation of metastases. These cells carry a number of defined markers: they are cd133 and cd44+kve and express high levels of 0(201 integrin. In this study we have, for the first time, assessed matched primary and bone marrow biopsies from prostate cancer patients for the distribution of cells carrying these and a number of other putative stem cell markers. METHODS. Eleven matched (primary and bone metastasis) specimens from prostate cancer patients were assessed for the presence of cd133, cd44, alpha 2 beta 1 integrin, CXCR4, c-met, c(6 integrin, and nestin using immunohistochemistry and stain intensity and distribution scored. RESULTS. In the bone metastases, tumor cells staining positively for cd133 were detected at low frequency in similar to 50% of samples. Staining for nestin was confined to endothelium. Positive staining of tumor cells for the other antigens was present at variable frequency in >70% of metastases with the exception of CXCR4 which was absent from all but 2 specimens. Where positive staining of tumor cells was present in the metastasis, cells staining for each antigen were present in the matched primary with the exception of cd44 which was absent in all but 2/11 matched primary tissues. CONCLUSIONS. In established metastases no single or combination of marker expression profiles identify the established metastatic phenotype, although cd44 expression was shown to be more frequent in metastases that in primary cancers. Prostate 70: 875-882, 2010. (C) 2010 Wiley-Liss, Inc. Show less
