Cancer stem cell definitions and terminology: the devil is in the details

Abstract

| The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients. PERSPECTIVES NATURE REVIEWS | CANCER VOLUME 12 | NOVEMBER 2012 | 767

Synthetic tambjamine analogues induce mitochondrial swelling and lysosomal dysfunction leading to autophagy blockade and necrotic cell death in lung cancer

“…This tumour subpopulation possesses tumour-initiating and self-renewal capacities, and contributes to acquired chemotherapy resistance in cancer [25], thus these results are very promising for lung cancer treatment and the prevention of tumour recurrences. In this view, other anionophores such as the recently reported 2-pyrrolylindole tambjamine analogues or the cation selective ionophore salinomycin, also induce CSCspecific toxicity [20,26], indicating that the application of these kind of compounds might be a very promising therapy.…”

“…Cells (1 × 10 5 cells/mL) were seeded in 96-well microtiter plates and incubated for 24 h to allow cells to attach. Afterwards, they were treated for 24 h with 10 µM of each compound for single point experiments and doseresponse curves were performed ranging from 0.78 to 100 µM to calculate the inhibitory concentrations of 25%, 50% and 75% of cell population (IC 25 independent experiments were performed and mean ± SD is shown.…”

“…A549 cells (1 x 10 5 cells/mL) were seeded and allowed to grow for 24 h. Afterwards, they were exposed to compounds (IC 25 …”

“…At very low concentrations of compound 2 (IC 25 ), an impressive appearance of the lipidated LC3 form (LC3-II), indicative of autophagosome formation (Figure 7c), was detected. On the other hand, p62, a protein that is itself degraded by autophagy, was not degraded but accumulated after treatment, indicating a blockade of the autophagic flux.…”

Cancer stem cells and addicted cancer cells

“…Currently, the widely accepted definition of CSCs is 'a cell within a tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor' [38]. Valent and colleagues [39] proposed a more detailed description for CSCs. Neoplasia is a term used to describe all situations where abnormal division or growth of cells occurs.…”