April 7, 2015 | by Darrin Joy
Neural stem cells have a natural ability to seek out cancer cells in the brain. Recent research from the laboratories of Michael Barish, Ph.D., and Karen Aboody, M.D., may offer a new explanation for this attraction between stem cells and tumors.
Prior to joining City of Hope, Aboody, now a professor in the Department of Neurosciences and the Division of Neurosurgery, found that neural stem cells are able to home in on invasive brain tumors. Since then, she and her colleagues have harnessed this ability to target cancer cells in a clinical trial at City of Hope, delivering localized chemotherapy directly to the most lethal form of brain cancer, high-grade gliomas. However, the specific drivers behind the stem cells’ ability to find tumors remain elusive.
The latest study, led by Patrick Perrigue, a former graduate student mentored by Aboody and Barish, points to a protein called Jumonji, expressed in both normal and cancer cells, as a key factor.
Jumonji tweaks the process of gene expression, causing key genes to turn on or off. Some of these genes are normally involved in immune activation, others in injury repair, and some in cellular aging. Tumor cells over-produce Jumonji, resulting in high production of molecules involved in inflammation and recruitment of immune cells.
“There is a notion that cancer can be thought of as ‘wounds that do not heal,’” Barish said. “Jumonji normally turns off during wound repair and regeneration, but in brain tumor cells this does not appear to happen.” The bad news is that, left unchecked, these molecules can help tumors develop and progress. The good news is that they also attract neural stem cells and probably other therapeutic cells.
Now that the researchers have shed light on this process and the role of Jumonji, they can begin searching for ways to manipulate the system to devise more effective therapies.
“We’ve opened up this little universe of possibility,” Barish said. “Jumonji influences many cellular pathways, and we can use this information to develop new targeted therapies and optimize existing ones.” He said future research may center on finding which specific molecules neural stem cells use most when homing to tumors. They also may focus on the glioma cells, targeting those molecules that boost tumor development or progression.
The prognosis for glioma is dismal — less than 10 percent of patients live five years or longer — so every chance at improvement is welcome news.
Other scientists contributing to the study include Michael Silva (a former California Institute for Regenerative Medicine-supported Bridges to Stem Cell Research trainee), Charles Warden, Nathan Feng, Michael Reid, Daniel Mota, Lauren Joseph, Yangzi Isabel Tian, Carlotta A. Glackin, Margarita Gutova and Joseph Najbauer.
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