St. Jude team finds brain cancer secret

8 February 2007

Despite treatments that sometimes go on for years and involve surgery, irradiation and chemotherapy, about 40 percent of brain tumors return, and the consequences are often deadly.

St. Jude Children's Research Hospital scientists believe they took another step recently in learning why relapses occur. Even better, they have a new strategy for tackling the problem and possibly curing more patients. The work, which took about four years and focused on cancer stem cells from four different brain tumors, appeared in a recent issue of the scientific journal Cancer Cell.

Think of cancer stem cells as the evil twin of the normal stem cells, around which so much hope and controversy have swirled recently. While the body relies on a small number of normal stem cells for life-sustaining renewal and repair, cancer stem cells play a similar role for malignant tumors. They sustain tumors and have a unique ability to generate new ones. First isolated more than a decade ago in leukemia patients, cancer stem cells have since been identified in at least seven different types of cancer.

The St. Jude paper provides the first evidence of where the cells are found in brain tumors. Researchers tracked them to areas of the brain dubbed "niches" or "micro-environments" rich in the same blood vessels that nurture normal stem cells.  The work also provides the first evidence that, just like normal stem cells, the cancer cells are nurtured by chemicals secreted by the cells lining those blood vessels. Those findings provide new clues about how the cancer stem cells survive treatments as well as their possible vulnerabilities. "Our data indicate these niches might also protect (cancer stem cells) from chemotherapy and irradiation therapy. And that could explain why aggressive tumors rapidly produce new blood vessels and why brain tumors reappear following treatment," explained Dr. Richard Gilbertson. He is co-director of St. Jude's Neurobiology and Brain Tumor Program and the study's principal investigator. St. Jude researchers reported that when cancer stem cells were transplanted into mice, they formed new tumors almost twice as rapidly if blood vessel cells were transplanted with them.

Gilbertson said the makeup of the chemical secreted by cells from the blood vessel's lining -- the "million dollar question" -- must still be determined.

The work also reflects the evolution in the scientific understanding of tumor cells. "Cancer cells are more like normal tissue than we previously thought," Gilbertson said. Dr. Peter Dirks, whose expertise includes cancer stem cells and brain tumors, said the St. Jude study "suggests a new treatment strategy beyond simply targeting the cancer stem cells directly." Dirks, an associate professor of neurosurgery at The Hospital for Sick Children and the University of Toronto, was not part of the St. Jude research team.

Gilbertson noted that the next generation of cancer treatments will likely target both the small number of cancer stem cells that sustain the tumor as well as the rapidly expanding cells that make up its bulk.  Those strategies are already being tested in children and adults whose brain tumors returned following treatment.  Gilbertson said at least three studies are either under way or about to begin at St. Jude and other medical centers. They include drugs that work by choking off the tumor's blood supply. In this paper, the St. Jude investigators reported that in mice treated with two drugs that block formation of new blood vessels, the tumors shrank and the number of cancer stem cells plunged. "This strongly suggests that disrupting the blood vessels in brain tumors might block tumor growth" by disrupting cancer stem cell niches, Gilbertson said. That's important because the ability to make new tumors resides completely in the relatively small number of cancer stem cells, not in the bulk of the cells that make up the tumor.

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