Three Studies Point To The Existence Of Cancer Stem Cells

Thursday, August 2, 2012

Cancer Stem Cells
Image Source: G. Driessens
 Cancer Research
Research from three independent studies shows strong evidence for the existence of cancer stem cells. Studies undertaken on skin, brain and intestinal tumours all point to the formation and spreading of cancer stem cells. These studies are bolstering a long-debated idea: that tumours contain their own pool of stem cells that can multiply and keep fuelling the cancer, seeding regrowth.
Today the medical community is facing a compelling but controversial hypothesis that many tumours are fuelled by ‘cancer stem cells’ that produce cancer cells, just as ordinary stem cells produce normal tissues. Previous studies have tested this idea by sorting cells from a cancer biopsy into subsets on the basis of factors such as cell-surface markers, and injecting them into laboratory mice.

In principle, those cells that generate new tumours are the cancer stem cells. But sceptics point out that transplantation removes cells from their natural environment and may change their behaviour. “You can see what a cell can do, but not what cells actually do,” says Cédric Blanpain of the Free University of Brussels, who co-led a skin study.

In recent studies, three research groups have addressed this knowledge gap by using genetic techniques to track cells. Luis Parada at the University of Texas Southwestern Medical Center in Dallas, who led a brain study, and his co-workers began by testing whether a genetic marker that labels healthy adult neural stem cells but not their more specialized descendants might also label cancer stem cells in glioblastoma, a type of brain cancer. When they did so, they found that all tumours contained at least a few labelled cells, that the researchers believe are cancer stem cells.

Tumours also contained many unlabelled cells. The unlabelled cells could be killed with standard chemotherapy, but the tumours quickly returned. Further experiments showed that the unlabelled cells originated from labelled predecessors. When chemotherapy was paired with a genetic trick to suppress the labelled cells, Parada says, the tumours shrank back into “residual vestiges” that did not resemble glioblastoma.

Meanwhile, Hans Clevers, a stem-cell biologist at the Hubrecht Institute in Utrecht, the Netherlands, and his colleagues focused on the gut. They had previously shown that a genetic marker that labels healthy gut stem cells also labels stem cells in benign intestinal tumours, which are precursors of cancer. In their latest study, he and his team engineered mice to carry a gene for a drug-inducible marker that, when activated, causes labelled cells to make molecules that fluoresce one of four colours.

This experiment yielded single-colour tumours consisting of several cell types, suggesting that each tumour arose from a single stem cell. To check that stem cells continued to fuel the tumours, Clevers added a second, low dose of the drug, triggering a few of the stem cells to change colour. This produced streams of cells in the new colour, showing that stem cells were consistently producing the other cell types.

For the skin study, Blanpain and his group labelled individual tumour cells, without targeting stem cells specifically. They found that cells showed two distinct patterns of division: they either produced a handful of cells before petering out, or went on to produce many cells. Once again, the results pointed to a distinct subset of cells as the engine of tumour growth. What’s more, as tumours became more aggressive, they were more likely to produce new stem cells — which can divide indefinitely — and less likely to produce differentiated cells, which can divide only a limited number of times. That could be a key to halting tumour development early, says Blanpain. Rather than eradicating cancer stem cells, for example, therapies could try to coax them to differentiate into non-dividing cells.

The papers provide clear experimental evidence that cancer stem cells exist, says Robert Weinberg, a cancer researcher at the Whitehead Institute in Cambridge, Massachusetts. “They have made a major contribution to validating the concept of cancer stem cells,” he says. But cancer cells probably also act in more complex ways than those observed, he warns. For example, non-stem cells within the tumour might de-differentiate into stem cells.

The next step, the three groups say, is figuring out how the cells tracked in these experiments relate to putative cancer stem cells identified by years of transplantation studies. Researchers are already busy hunting for ways to kill these cells; now they have more tools to tell whether such a strategy will work. —

SOURCE  Nature

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