Evaluation of the frequency of putative prostate cancer stem cells in primary and metastatic prostate cancer
Eaton CL., Colombel M., Van Der Pluijm G., Cecchini M., Wetterwald A., Lippitt J., Rehman I., Hamdy F., Thalman G.
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 types within tumors and also for the initiation of metastases. These cells carry a number of defined markers: they are cd133 and cd44+ve and express high levels of α2β1 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, α2β1 integrin, CXCR4, c-met, α6 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 ̃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. © 2010 Wiley-Liss, Inc.