We would like to thank Olivier Gires, Christoph Klein and Patrick A. Baeuerle for their correspondence on our Review (Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nature Rev. Cancer 8, 755–768 (2008))1, which raises some important issues (On the abundance of EpCAM on cancer stem cells. Nature Rev. Cancer 15 Jan 2009 (doi:10.1038/nrc2499-c1))2.
We agree that epithelial cell adhesion molecule (EpCAM) has potential as a cancer stem cell (CSC) marker and that its name is best standardized to EpCAM (other names include ESA and Ber-EP4). As an almost pan-epithelial marker in some tissues, such as colon, it is difficult to estimate the importance of EpCAM as a marker of CSCs in solid tumours versus its role as a more general epithelial surface marker. Nevertheless, it is likely to be useful in the purification of some CSCs originating in epithelial tumours. Further studies are needed to define the status and role of EpCAM as a CSC marker, as the existing data are preliminary for breast and colorectal CSCs but appear more compelling for the pancreatic CSC. For pancreatic tumours, CD44, CD24 and EpCAM (referred to as ESA) together conferred a >100-fold increase in tumorigenic potential3. In the case of breast tumours, EpCAM led to considerable enrichment of CSCs in one breast tumour4, but was less useful in a second tumour, as both the EpCAM-positive and EpCAM-negative fractions from this tumour had tumorigenic activity. It is presumed that EpCAM did not lead to further enrichment in the other seven tumours examined. Interestingly, EpCAM is commonly used for the purification of circulating breast tumour cells5,6. In the context of colorectal CSCs, EpCAM was expressed on almost all tumour cells (both CD133+ and CD133−). In these studies, EpCAM expression was used to confirm that the high proportion of CD133− cells in xenografts corresponded to cancer cells of human epithelial origin7,8.
References
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Gires, O. Klein C. & Baeuerle, P. A. On the abundance of EpCAM on cancer stem cells. Nature Rev. Cancer 15 Jan 2009 (doi:10.1038/nrc2499-c1).
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Visvader, J., Lindeman, G. EpCAM and solid tumour fractionation. Nat Rev Cancer 9, 143 (2009). https://doi.org/10.1038/nrc2499-c2
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DOI: https://doi.org/10.1038/nrc2499-c2
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