More than markers: biological significance of cancer stem cell-defining molecules

Small populations within an increasing array of solid tumors, labeled cancer stem cells (CSC) or tumor-initiating cells (TIC), have the ability to differentiate, self-renew, and replicate the original tumor in vivo. To date, these cells have been distinguished from the bulk-tumor population by the expression pattern of cell-surface proteins (e.g., CD24, CD44, CD133) and cellular activities, such as the efflux of Hoechst dye or aldehyde dehydrogenase activity. Recent data have shown that these markers are inducible by exposure to anticancer agents; this finding highlights not only the potential fluidity of the CSC compartment, but also the functionality of these markers. The involvement of CD44 in invasion, adhesion, and metastasis, or the role of CD24 in modulation of src, FAK, and GLI1 are examples of these relevant roles. Instead of looking solely at the marker expression in these populations, we hope to clarify the biologically significant roles these markers and activities play in tumor progression, metastases, and as possible targets for therapy.