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Conversion of brain tumor cells into blood vessels thwarts treatment efforts
Date:1/24/2011

of cancer cells," explains Verma, "but in most patients this effect was only transient." In fact, studies have shown that tumor cells often become more aggressive after anti-angiogenic therapy, but the reason had been unclear.

To find out, postdoctoral researcher and first author Yasushi Soda, Ph.D., took advantage of a mouse model of glioblastoma that recapitulates the development and progression of human brain tumors that arise naturally. "The tumors in these mice closely resemble glioblastomas, including the typically messy and highly permeable tumor vessels, which allowed us to study the tumor vasculature in great detail," he explains.

The glioblastoma mice, the concept for which was developed in the Verma laboratory, grow brain tumors within a few months of being injected with viruses that carry activated oncogenes and a marker gene that causes all tumor-derived cells to glow green under ultraviolet light. By simply tracking the green glow under the microscope, the Salk researchers can then follow the fate of tumor cells.

When Soda peered at the tumor cells, he found--much to his surprise--that about 30 percent of vascular endothelial cells--specialized cells that line the interior surface of blood vessels--appeared green. "This indicated to us that they most likely originated from tumor cells," he says.

Further experiments revealed that TDECs, short for tumor-derived endothelial cells, are not specific to mouse tumors but can also be found in clinical samples taken from human glioblastoma patients. "This was really strong evidence for us that glioblastoma cells routinely transdifferentiate into endothelial cells," he explains.

The transformation is triggered by hypoxia, or low oxygen levels, which signals tumor cells that the time has come to start their shape-shifting stunt. But unlike regular vascular endothelial cells, TDECs don't require VEGF to form functional blood vessels. "This might explain why, despite bei
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Contact: Gina Kirchweger
Kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert  

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