Sacking Cancer Stem Cells

Starving the source.
Cancer stem cells (dark purple) reside near capillaries and give rise to normal tumor cells (light purple). They die when drugs target the capillary blood supply (bottom).

Credit: Cancer Cell

Scientists have found the Achilles' heel of cells that jump start tumor growth. According to a new study, these "cancer stem cells" reside in blood vessels. Disrupting these vessels, say the researchers, may prove a far more effective cancer therapy than targeting other regions of a tumor.

Cancer biologists once believed that all cells in a tumor were pretty much the same. But in the early 1990s, a team found some interesting characters hanging out with leukemia cells: Instead of rapidly dividing like their million-fold-more-plentiful companions, these outliers grew slowly. And when transplanted to a petri dish, they gave rise to the more common type of leukemia cell. Cancer stem cells are the ultimate source of the tumor, consistently supplying it with new cells. Since then, researchers have discovered other cancer stem cells, including those behind acute myeloma leukemia, two types of brain cancer, and breast cancer. Killing these stem cells should allow researchers to hit a tumor where it hurts, yet chemotherapy has proven ineffective as it tends to kill only rapidly dividing cells.

So neurobiologist Richard Gilbertson at St. Jude Children's Research Hospital in Memphis, Tennessee, and colleagues began looking for a weakness. They started by comparing cancer stem cells to noncancerous neural stem cells. These neural tissue precursors are concentrated in regions rich in blood vessels. The vessels are lined with endothelial cells, which secrete chemical signals that help stem cell survive. Gilbertson's team wondered whether cancer stem cells might require a similar niche.

Sure enough, after examining over 70 human brain tumors, the researchers found that cancer stem cells were frequently located close to tiny vessels called capillaries. When the researchers injected mice with a mix of stem and endothelial cells from human brain tumors, the animals sprouted larger tumors than did mice receiving stem cells alone, the team reports today in Cancer Cell. Drugs that shrunk the capillaries also caused a significant drop in cancer stem cells and consequently put a damper on tumor growth. The same drugs hardly affected the survival of cells in rest of the tumor.

"This study is an excellent example of bringing stem cell insight to cancer," says Robert Wechsler-Reya, a cancer biologist at Duke University Medical Center in Durham, North Carolina. "I think this is going to be the beginning of a really popular approach [to cancer therapy]."

Antiangiogenic agents as cancer treatment are interesting and promising. The article correctly identifies that antiangiogenic agents kill the cancer cells. The proximal stem cells enhancing tumor growth (and their subsequent demise eliminating it) is an interesting bit of information.

Another interesting fact is that antiangiogenic agents, contrary to intution, enhance the effectiveness of cytotoxic (chemotherapy) agents by increasing their concentration in the tumor. This according to research by Dr. Bevery Teicher.

Thanks for posting these very interesting articles.

Fascinating stuff. Have multiple friends and family (in-laws) undergoing cancer treatment right now. This will most likely be too late for some of them, but it gives me hope for the future.

You may have followed the media hype surrounding Endostatin and Angiostatin in 1999 - the culmination of the life's work of Dr. Judah Folkman.

Though Entremed terminated Endostatin production in 2003 due to the extremely high cost a Chinese researcher, Dr. Luo Yongzhang, has identified the molecule, mastered the protein folding technique, and his company is now producing its own version, Endostar, at cheaper production costs (link).

It is a very exciting area of cancer research.

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