Cancer stem cells (CSCs) are supposed to be self-renewing, but current knowledge says that these cells are only a tiny part of most brain tumors. The natural assumption then is that they are insignificant. But new research appearing in the January 2007 issue of the journal Cancer Cell, published by Cell Press, says that eliminating these cancer stem cells plays a vital role in the eventual survival as well as growth of a brain tumor. 

The study reveals that tiny blood vessels create a sound microenvironment that is vital for the survival of cancer stem cells. Hence antiangiogenic drugs, which disrupt the microenvironment created by these blood vessels, might be the answer to controlling the population of cancer stem cells.

The new study by Dr. Richard J. Gilbertson and colleagues from the St. Jude Children's Research Hospital proved that CSCs in human brain tumors are fed by these minor blood vessels and are able to even maintain brain CSCs in laboratory cultures.

To examine whether the vessel-derived factors promote maintenance of CSCs and tumor propagation in vivo, the researchers transplanted human brain tumors into mice with or without vascular cells. The mice with extra vascular cells exhibited an increase in CSCs as well as enhanced initiation and proliferation of tumors. The authors also found that when antiangiogenic therapies were used to diminish tumor blood vessels, CSCs were reduced and tumor growth was arrested, further supporting the importance of the vascular microenvironment to CSCs.

"Our data identify a possible role for niche microenvironments in the maintenance of CSCs and identify a mechanism by which antiangiogenic drugs inhibit brain tumor growth," concludes Dr. Gilbertson. "If the notion that niches protect CSCs proves correct, then targeting these microenvironments could prove highly effective treatments of cancer." Further research and clinical trials are needed to investigate this important new mechanism associated with antiangiogenic cancer therapies. It seems likely that effective cancer treatments must target both the bulk of rapidly proliferating tumor cells and the smaller population of self-renewing CSCs.


                                                                        ###
The researchers include Christopher Calabrese, Helen Poppleton, Mehmet Kocak, Twala L. Hogg, Christine Fuller, Blair Hamner, Eun Young Oh, M. Waleed Gaber, David Finklestein, Meredith Allen, Adrian Frank, Ildar T. Bayazitov and Stanislav S. Zakharenko, Amar Gajjar, Andrew Davidoff and Richard J. Gilbertson of St. Jude Children's Research Hospital in Memphis, TN.

This work was supported by the Sontag Foundation ( R.J.G. ), NCI grant CA096832 ( R.J.G. ), the V-Foundation for Cancer Research ( R.J.G. ), and the American Lebanese Syrian Associated Charities ( ALSAC ).

Calabrese et al.: "A Perivascular Niche for Brain Tumor Stem Cells." Publishing in Cancer Cell 11, 69–82, January 2007. DOI 10.1016/j.ccr.2006.11.020 http://www.cancercell.org