Coddling cancer

JCB • VOLUME 176 • NUMBER 4 • 2007 374 Coddl ing cancer T he brain pampers not just its normal stem cells, but also the cancer stem cells responsible for most tumor growth, report Christopher Calabrese, Richard Gilbertson (St. Jude Children’s Research Hospital, Memphis, TN), and colleagues. The study is the fi rst to demonstrate that tumors contain a stem cell niche and may help researchers devise ways to evict the cells from their cushy digs. Neighboring cells cradle stem cells within a structure termed a niche. Besides providing protection, niche cells release factors that maintain stem cells’ ability to divide. But researchers weren’t certain whether cancer stem cells (CSCs) also reside within niches in tumors. Using multiphoton laser scanning microscopy, Gilbertson and colleagues observed that CSCs adhere to capillaries within brain tumors, suggesting that the vessels fashioned a niche. To determine whether this interaction was vital for cancer growth, the researchers nurtured balls of CSCs in partitioned wells that allowed the cells to exchange molecules with—but not touch—other cell types. CSC spheres cultivated with endothelial cells grew faster than did CSCs reared with control cells. Gilbertson and colleagues also gauged whether niche cells control CSCs’s ability to seed new tumors by injecting cell mixtures into the brains of immune-defi cient mice. The combination of CSCs and endothelial cells spawned enough tumors to kill the rodents within four weeks, versus seven weeks for CSCs alone. The scientists then implanted CSCs into the brains of mice and treated the animals with two types of antiangiogenesis drugs. The medications reduced the density of capillaries in the implants and slashed the rate of tumor growth by removing CSCs. “The immediate microenvironment is likely to be generating or maintaining CSCs,” says Gilbertson. What researchers don’t understand, he adds, is why the niche for CSCs promotes rampant cell division, whereas the niche for normal stem cells encourages more leisurely growth.