Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization

Primary tumors are responsible for 10%of cancer deaths. In most cases, the main cause ofmortality is the formation of metastases. Accumulatingevidence suggests that a subpopulation of tumor cells withdistinct stem-like properties is responsible for tumorinitiation, invasive growth, and metastasis formation. Thispopulation is defined as cancer stem cells (CSCs). Existingtherapies have enhanced the length of survival afterdiagnosis of cancer but have completely failed in terms ofrecovery. CSCs appear to be resistant to chemotherapy,may remain quiescent for extended periods, and haveaffinity for hypoxic environments. The CSCs can beidentified and isolated by different methodologies, includingisolation by CSC-specific cell surface markerexpression, detection of side population phenotype byHoechst 33342 exclusion, assessment of their ability togrow as floating spheres, and aldehyde dehydrogenase(ALDH) activity assay. None of the methods mentionedare exclusively used to isolate the solid tumor CSCs,highlighting the imperative to delineate more specificmarkers or to use combinatorial markers and methodologies.This review provides an overview of the maincharacteristics and approaches used to identify, isolate,and characterize CSCs from solid tumors.—Tirino, V.,Desiderio, V., Paino, F., De Rosa, A., Papaccio, F., LaNoce, M., Laino, L., De Francesco, F., Papaccio, G.Cancer stem cells in solid tumors: an overview and newapproaches for their isolation and characterization.FASEB J. 27, 000–000 (2013). www.fasebj.org