Studies support notion that stem cells create, re-create cancers
New evidence from three independent studies supports the idea that solid tumors in the brain, colon and skin can arise from a few bad cells known as cancer stem cells.
Cancer researchers have debated whether every cell in a tumor is capable of re-creating the tumor, or if only a few special cells have that capacity. To answer the question, researchers have transplanted tumor cells from human cancers into mice, producing mixed results.
Now, in separate attempts to settle the issue, three research groups have taken a similar approach: tagging mouse cells with fluorescent proteins to trace various cells’ fates as tumors develop within the animal’s body. In each case, tumors seem to arise from a small group of cells that act like stem cells, researchers report online August 1 in Nature and Science. Cancer stem cells are thought to be able to re-create tumors the way that normal stem cells replenish tissues.
While the studies don’t definitively demonstrate that only cancer stem cells are capable of re-creating tumors, the three papers are signposts pointing to the direction research should go, says Phil Jones, a stem cell biologist at the Hutchison/MRC Research Centre in Cambridge, England. Researchers investigating cancer stem cells need to move away from the transplant experiments and study cancer cells in their native environments, Jones says.
In one study, researchers found that about 20 percent of cells in benign skin tumors called papillomas are a type of rapidly growing cell. But skin cancers called squamous cell carcinomas have a much higher proportion of these purported stem cells, Gregory Driessens of the Université Libre de Bruxelles in Belgium and colleagues report in Nature. The finding could mean that for tumors containing large numbers of cancer stem cells, it may appear as if any cell in the tumor can cause a recurrence of the cancer, Driessens says.
While squamous cell skin cancers may be densely populated by cancer stem cells, a deadly type of brain tumor called glioblastoma multiforme relies on only a small pool of such cells to generate the tumor, researchers led by Luis Parada, a molecular geneticist at the University of Texas Southwestern Medical Center in Dallas, report in Nature. Parada’s team genetically engineered mice to make green fluorescent protein in all stem cells in the brain. The mice also carried three genetic mutations that cause some normal brain stem cells to develop into glioblastomas. A chemotherapy drug called temozolomide killed dividing cells in the tumor, but didn’t eliminate the cancer stem cells, which are mostly dormant but have bursts of growth. When chemotherapy stopped, the stem cells began to divide and caused the tumor to grow again.
The finding suggests that the only way to cure this type of cancer is to kill the stem cells, Parada says. And doctors may need to re-evaluate how they measure a cancer treatment’s success. “A shrinking tumor doesn’t necessarily mean an efficacious therapy,” he says.
A third study, published online in Science, shows that a benign colon tumor called an adenoma grows from stem cells normally responsible for replacing intestinal cells. “The tumor is really a caricature of the normal situation,” says study coauthor Hugo Snippert, a molecular geneticist at the University Medical Center Utrecht in the Netherlands.
J. Chen et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. doi:10.1038/nature11287.
G. Driessens et al. Defining the mode of tumour growth by clonal analysis. Nature.c i:10.1038/nature11344.
A.G. Schepers et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science. doi: 10.1126/science.1224676.
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