Study Identifies Cancer Stem Cell “Incubators”
2/26/2007


A study recently published in Cancer Cell* yields compelling new data about the origins of the four most common types of brain cancer, as well as information about two drugs that show promise for treating tumors of all kinds.

All Cancer Cells are Not Created Equal

First, a bit of background. Our understanding of cancer has progressed dramatically in the last ten years, says the study's primary investigator, Richard J. Gilbertson, MD, PhD, of St. Jude Children's Research Hospital.

“In particular, we now have firm evidence that all cancer cells are not equal – that different cells do different things and function in a hierarchy,” Gilbertson says. “We now believe that only about one percent of the cells in a tumor possess the ability to divide endlessly to create the tumor and fuel the cancer.”

Although the other 99 percent of tumor cells are important in their own ways, the cancer stem cells (CSCs) that make up that one percent are the ones that promote the tumor growth, which is key when it comes to cancer. Tumors growing unchecked eventually hinder the function of critical organs, which is why cancer makes us sick and can ultimately be fatal.

“Tumors are more like normal tissues than we previously realized, and there are many parallels between the cells of a malignant brain tumor and normal brain cells,” he says. “And just as normal cells arise from normal stem cells, we think cancer cells arise from cancer stem cells – which has huge ramifications for understanding and treating tumors.”

Significant Parallels, an Important Discovery

Gilbertson's team, which looked at more than 80,000 cells from the four most common types of brain tumors (medulloblastoma, ependymoma, oligodendroglioma and glioblastoma), sought to confirm the existence of one parallel in particular: whether the same highly specialized, carefully controlled environments known to foster the creation and growth of normal stems also exist in brain tumors, generating CSCs.

These environments, known as vascular niches, are miniscule anatomical units that occur in and near blood vessels, serving as incubators of sorts for normal stem cells. In other words, these niches are critical to stem cell development.

The question Gilbertson's team asked was, “Do the cancer stem cells in brain tumors also exist in these specialized niche environments?” The answer, they learned, is yes.

“We discovered CSCs in all four types of tumors – always adjacent to and dependent upon blood vessels, which they need to survive,” he says. “It's of course important to our study of brain tumors, but it's also the first time these abnormal vascular niches have been demonstrated in tumors in general.”

Anti-Angiogenesis Drugs Show Promise

Another of the study's more compelling findings involves Erlotinib and Bevacizumab, drugs with anti-angiogenic properties that block the proteins that make blood vessels grow. When the vascular niches that are home to the brain CSCs were targeted with these drugs, Gilbertson says, “the cancer stem cells disappeared – presumably because they could no longer survive. As a result the whole tumor stopped growing.”

These findings have sparked renewed enthusiasm about the uses of anti-angiogenic drugs.

“Our study suggests a completely new way these drugs might be used, and that's causing great interest right now,” Gilbertson says. “Even though people have been studying them and using them in clinic for several years, sometimes they work and sometimes they don't, and nobody really knows why.” Studies suggest it's far more complicated than simply cutting off the blood supply to tumors, he says.

If additional research confirms that tumor cells are derived entirely from CSCs, drugs that minimize toxicity by destroying only the blood vessels that feed CSCs have the potential to be effective cancer treatments.

Although St. Jude treats only children, Gilbertson noted that clinical trials involving anti-angiogenic drugs are currently underway among adult cancer patients.

Article
* Calabrese C, et al., A perivascular niche for brain tumor stem cells. Cancer Cell. 2007 Jan;11(1):69-82.



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