Over the past four decades researchers have made great progress in the War against Cancer, a disease that one in three women and half of men are at risk of developing during their lifetime.
Cancer researchers have learned to sequence cancer cells’ genomes, scan the cells for suspicious gene activity, profile the contents for symptomatic proteins and watch them grow in a petri dish.
What they haven’t been able to do, until now, is track cancer cells as they form new tumors.
A new article in Nature has added support to the idea that tumor growth is driven by a small subset of “cancer stem cells”. The studies, done in mice by three international groups, may be one of the biggest breakthrough in cancer research to date.
If it turns out this compelling but controversial hypothesis is correct for all cancer types, eliminating those cells could be the answer to curing cancer.
Just as ordinary stem cells produce normal tissues, some cancer researchers believe tumor development is fueled by cancer stem cells.
Previous studies have tested this idea by sorting cancer cells into subsets and injecting them into laboratory mice. The idea is, if cells generate new solid tumors they can be classified as cancer stem cells.
But some researchers reject the notion of cancer stem cells altogether.
Critics quickly point out that transplantation alters cells’ natural environment and thus, may change the cells' behavior. These experts say it's possible that cancer cells may act in far more complex ways than those observed.
It’s too soon to know if the results for brain cancer, gastric cancer and skin cancer will hold true for other cancer types, said Dr. Luis Parada, a developmental biologist at the University of Texas Southwestern Medical Center in Dallas, who led the brain study.
But if it does, “there is going to be a paradigm shift in the way that chemotherapy efficacy is evaluated and how therapeutics are developed.”
Parada told Nature that instead of testing to see if a treatment shrinks a tumor, researchers will assess whether it kills the right sorts of cell.
All three groups used genetic techniques to track cells in different primary tumor types.
Glioblastoma Multiforme Brain Cancer
Parada’s group tested to see whether or not a genetic marker that labels healthy adult neural stem cells, but not their more specialized descendants, might also label cancer stem cells in glioblastoma multiforme, a common type of brain cancer that is generally aggressive and deadly.
Researchers found all tumors studied contained at least a few labeled cells which they presumed were stem cells. The tumors also contained many unlabeled cells that were killed with standardized chemotherapy, but these tumors quickly returned.
In subsequent experiments, the researchers found that unlabeled cells originated from labeled predecessors. When chemotherapy was paired with a genetic trick to suppress the labeled cells, Parada said, the tumors shrank back into “residual vestiges” that did not resemble glioblastoma.
Gastric Cancer
Hans Clevers, a stem-cell biologist at the Hubrecht Institute in Utrecht, Netherlands, and his colleagues focused on cancers of the gastrointestinal (GI) tract.
Their previous research had shown that a genetic marker which labels healthy GI stem cells also labels stem cells in benign intestinal tumors, a precursor of cancer.
In their latest study, Clevers’ team engineered mice to carry a gene for a drug-inducible marker that, when activated, causes labeled cells to make molecules that fluoresce one of four colors.
This experiment yielded single-color solid tumors consisting of several cell types, suggesting that each tumor arose from a single stem cell, according to Nature.
Just to be sure the stem cells were continuing to fuel tumor growth, Clevers added a second, low dose of the drug, triggering a few of the stem cells to change color. This produced streams of cells in the new color, showing that stem cells were constantly renewing and consistently producing other cell types.
Skin Cancer
Cédric Blanpain of the Free University of Brussels, co-led the skin study. His group labeled individual tumor cells, without targeting stem cells specifically, and found that cells showed two distinct patterns of division.
They either produced a handful of cells before burning out, or went on to produce many cells.
As in the other studies, these results point to a distinct subset of cancer stem cells fueling tumor growth.
As these tumors became more aggressive, new stem cells formed. Unlike differentiate cells, which divide only a limited number of times, cancer stem cells are believed to be capable of dividing indefinitely.
As Blanpain told Nature, this could be the key to halting tumor development early. One example might be that, rather than eradicating cancer stem cells, treatment therapies could try to direct the cells to differentiate into non-dividing cells.
The three groups’ next step is to figure out how the cells tracked in these studies relate to cells in other cancer types identified by years of transplantation studies. Researchers are already busy looking for ways to kill these cells and now have new tools to help them with their endeavor.
Lynette Summerill is an award-winning writer and Scuba enthusiast living in San Diego, CA with her husband and two beach loving dogs. In addition to writing about cancer-related issues for EmpowHER, her work has been seen in newspapers and magazines around the world.
Sources and Information:
National Cancer Institute. Cancer Facts and the War on Cancer. 6 August 2012. Online at:
http://training.seer.cancer.gov/disease/war
Nature. ‘Cancer Stem Cells Tracked’ Monya Baker, 2 August 2012, 488, 13–14 doi:10.1038/488013a
http://www.nature.com/news/cancer-stem-cells-tracked-1.11087
http://www.nature.com/nature/focus/cancerstemcells
Study suggests new treatment target for deadly brain tumors. UT Southwestern Medical Center. 1 Aug. 2012. Online at
http://www.utsouthwestern.edu/newsroom/news-releases/year-2012/august/glioblastoma-parada.html
Wnt signaling and cancer. Hubrecht Institute. Access information and videos online at:
http://www.hubrecht.eu/research/clevers/research.html
Cancer and Stem Cells. Free University of Brussels news. February 8, 2012. (L’article En Français)
http://www.ulb.ac.be/actulb/index.php?e=2633&page=0#2633
Reviewed August 14, 2012
by Michele Blacksberg RN
Edited by Jody Smith