Is CD44 a Marker for Cancer Stem Cells?
CD44 is a cell surface transmembrane glycoprotein involved in cell adhesion and migration, and also the regulation of numerous intracellular signalling events. As well as the ubiquitously expressed standard form, alternative splicing and post-translational modification give rise to numerous variant isoforms. Altered expression of CD44 occurs in cancer, particularly in association with invasion and metastasis. More recently the molecule has received considerable attention as a potential marker of cancer stem cells (CSC). The CD44+ fraction of numerous tumours has been reported to demonstrate enhanced tumourigenic potential and the ability to recapitulate the parental tumour. Blockade of CD44 may therefore represent a means of eliminating the putative tumour-propagating CSC fraction of some tumours.
However, CD44 is not a universal marker of CSC. More fundamentally, some evidence suggests that the CD44+ CSC phenotype could be unstable, or even acquired by cells within the CD44− fraction, questioning the concept of CD44+ cancer cells existing at the apex of a unidirectional developmental hierarchy. Moreover, any notion of targetting CD44 will be complicated by its widespread expression on normal cells. Thus, although many features of CD44 make it an attractive candidate as a CSC marker, there is need for a greater understanding of the significance of expression, and in particular the expression of variant isoforms, in the context of putative cellular hierarchies in cancer.
KeywordsCancer Stem Cell Clonal Evolution Normal Stem Cell Cancer Stem Cell Marker Cancer Stem Cell Population
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