There is no previous information on the nature of cancer stem-like cells in small-cell lung cancer. The aggressive nature of SCLC combined with the capacity for differentiation into multiple lineages and the development of resistant disease suggest that this tumour may be enriched in cells with cancer stem cell-like characteristics.
It has high proliferative capacity, with a doubling time estimated to be as fast as 38 days in humans ( Sone et al, 2007). Small-cell lung cancer is a neuroendocrine tumour composed of cells capable of differentiation into neuronal and endocrine lineages, thus bridging two unrelated organ systems. These patients usually present with disseminated disease to many organs, including the brain, and their initial response to therapy is rapidly followed by a relapse with drug-resistant disease. In spite of recent decline in frequency, it still accounts for approximately 12% of the 220 000 new lung cancer cases projected for 2009 ( Jemal et al, 2009). Small-cell lung cancer (SCLC) is the most devastating type of human lung cancer. This gene signature may be used for development of targeted therapies for this rapidly fatal tumour. Side population cells from SCLC are highly enriched in tumourigenic cells and are characterised by a specific stem cell-associated gene expression signature. Whereas non-SP cells formed fewer and slower-growing tumours, SP cells over-expressed many genes associated with cancer stem cell and drug resistance: ABCG2, FGF1, IGF1, MYC, SOX1/2, WNT1, as well as genes involved in angiogenesis, Notch and Hedgehog pathways. In contrast, as few as 50 SP cells from H146 and H526 SCLC cell lines rapidly reconstituted tumours. Previous reports indicated that several thousand SP cells from non-small-cell lung cancer are required to form tumours in mice.
Side population cells have higher proliferative capacity in vitro, efficient self-renewal and reduced cell surface expression of neuronal differentiation markers, CD56 and CD90, as compared with non-SP cells. We examined several SCLC cell lines and found that they contain a consistent SP fraction that comprises <1% of the bulk population. These features suggest enrichment in cancer stem cells. Small-cell lung cancer (SCLC) is a highly aggressive human tumour with a 5-year survival rate of <10%. The relationship between SP cells, drug resistance and cancer stem cells is poorly understood. Side population (SP) fraction cells, identified by efflux of Hoechst dye, are present in virtually all normal and malignant tissues.
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