Cancer Research Lab

Brain cancer stem cells are maintained within vascular niches. Although these cells may be resistant to conventional treatment, preliminary studies suggest that antiangiogenic drugs can block tumor growth.

“Cancers share more properties of normal developing tissues than we may have appreciated,” Dr. Richard J. Gilbertson from St. Jude Children’s Research Hospital, Memphis, Tennessee said. “This work opens up new avenues for treatments, but suggests also that we need to work hard to define truly how cancers and normal tissues differ.”

Dr. Gilbertson and associates investigated whether brain tumor stem cells develop within niche microenvironments in the brain vasculature. The majority of cancer stem cells in brain tumors were closely associated with tumor capillaries, the authors report in the January issue of Cancer Cell.

In vitro, brain tumor stem cells associated rapidly with endothelial vascular tubes, forming close contacts along their lengths, the results indicate. Further experiments showed that endothelial cells maintained self-renewing and undifferentiated brain tumor cells and promoted the propagation of brain tumors in vivo.

Depletion of brain tumor blood vessels effectively eradicated the population of self-renewing tumor cells, the report indicates. This led investigators to propose “that antiangiogenic drugs arrest brain tumor growth, at least in part, by disrupting a vascular niche microenvironment that is critical for the maintenance of cancer stem cells.”

“We are currently dissecting the various cellular and protein components of the niche to identify the critical parts that maintain cancer stem cells,” Dr. Gilbertson said. This may help identify new therapeutic targets.

This work “highlights the importance of the vascular microenvironment in brain tumor growth,” write Dr. Zeng-Jie Yang and Dr. Robert J. Wechsler-Reya from Duke University Medical Center, Durham, North Carolina, in a related commentary.

“Similarly, the finding that disruption of angiogenesis leads to a reduction in growth of fully formed tumors suggests that the vascular niche may also be critical for tumor maintenance.”

“The notion that antiangiogenic therapy targets cancer stem cells has important implications for evaluating and optimizing the use of antiangiogenic drugs in cancer,” they conclude.