Cancer stem cells resemble healthy stem cells, resist chemotherapy

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Two papers show how tumour-initiating cells work, and why they're hard to treat.- A, H6 Y1 @7 h
Researchers led by Jenny Chang at Baylor College of Medicine in Houston found a characteristic signature in a group of tumour cells remaining in a patient after treatment for breast cancers.1 These resistant cells were enriched whether patients underwent chemotherapy or were given drugs that block the action of tumour-promoting sex hormones, suggesting that there is a particular population of cells that can resist treatment and cause the tumour to regrow. Chang found that the gene expression in this subpopulation overlapped with two other sorts of cells: those that readily perpetuate tumours and those that allow cells to self-renew over long periods in culture. What's more, these resistant cells may also be responsible for the spread of cancer outside the breast. Cells with this gene expression are particularly dominant in a relatively uncommon cancer called "claudin-low," which displays characteristics of undergoing a process called the epithelial–mesenchymal transition (EMT), implicated in the spread of a malignancy. Similarly, cells remaining in tumours that had been treated with an estrogen-blocking drug showed elevated expression of mesenchymal markers. Homing in on unique characteristics of these cells may, says Chang, allow researchers to identify drugs that could eliminate these cells.3 q( i2 I5 J1 _5 y& J# ?5 l2 s& \8 \
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Just a few days later, researchers led by Michael Clarke of Stanford University tried a different approach to identify regulatory pathways in breast cancer stem cells. This work showed that these stem cells are governed by the same regulatory pathways as their healthy counterparts, mammary stem cells. The researchers were able to isolate cancer stem cells from human samples and perform analysis on small quantities of cells.2 This identified some three dozen microRNAs differentially expressed between tumourigenic cells and other cells in the tumour. The researchers also compared tumourigenic cells with normal mouse and human mammary stem/progenitor cells as well as embryonal carcinoma cells. Three clusters of microRNA were downregulated in all these cell types, one of which was miRNA-200c, previously found to regulate the epithelial–mesenchymal transition. Elevating levels of this microRNA suppressed self-renewal and encouraged differentiation in both normal and cancerous breast stem cells. Further work showed that this microRNA controls levels of a well-known protein called BMI1, which also regulates stem cells of the blood and brain. Thus, it seems, stem cell functions such as self-renewal, proliferation and EMT all seem to be governed by similar mechanisms—not just in healthy and disease tissue, but across different types of tissues.

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