For more than a decade, scientists have hypothesized that cancer stem cells, small populations of stem cells within tumors, fuel the lesions' development and cause renewed tumor growth months or years after radiation or chemotherapy. The cancer stem cell hypothesis has remained controversial because of the inconclusive experiments and results that supported it. But now, researchers have added new evidence in favor of the hypothesis.
In their study, Snippert and collaborators color-coded cells in the intestines of mice to determine which ones formed adenomas, a precursor to intestinal cancer. Tracking candidate stem cells in the adenomas, the team showed that the cells were fast-growing, generated different cell types within the tumor, and were located at somewhat similar positions as healthy stem cells in healthy tissue. The team published its findings online Aug. 1 in Science (1).
In addition, two other papers supporting the cancer stem cell hypothesis appeared online Aug. 1 in Nature (2,3). Taken together, the results suggest that this population of stem cells within tumors could be targeted to improve scientists' understanding of tumor growth and future cancer treatments.
In the Science paper, Snippert and collaborators report that intestinal cancer cells grow from cells that express a gene called Lgr5+. Normal intestinal stem cells also express this gene. To understand the differences in expression and cell growth, the team used a multicolored reporter, which created a genetic marking and then a color-code for specific cells. "That same marking is inherited by all the cells that are derived from that original cell from that moment onwards," said Snippert.
The markings came in four colors: green, yellow, red, or blue. When the scientists induced tumor growth in mice intestines, the cell from which the tumor originated picked one of the four colors to mark itself. As a result, the whole tumor had the same color at first. But once the tumor got established, the cancer stem cells could re-pick a new color.
"From that moment onward there was a chance that cancer stem cells would produce offspring with a blue color in the background of a red tumor. This allowed us to study the behavior of cancer stem cells within their own endogenous tumor environment," said Snippert.
Because of the multi-colored patterns in the mice's cells, the team called their animals "confetti mice." Tracking the expression of the colors, the scientists discovered that the stem cells' offspring developed into multiple cell types and that clones of the cells grew much faster in number compared to the division rate in the bulk of the tumor.
The two other studies published in Nature used similar genetic cell-marking techniques. Both showed that most of tumor growth in skin and brain tissue came from a specific subset of cells within the tumor.
Now that scientists have shown that cancer stem cells exist, "it is essential that this population of cells be targeted" in future research and treatments of cancer, said Snippert.
1. Schepers, A., et. al. 2012. Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas. Science Express. http://www.sciencemag.org/content/early/2012/07/31/science.1224676.full
2. Chen, J., et. al. 2012. A restricted cell population propagates glioblastoma growth after chemotherapy. http://dx.doi.org/10.1038/nature11287
3. Driessens, G. et. al. 2012. Defining the mode of tumour growth by clonal analysis. Nature. http://dx.doi.org/10.1038/nature11344