The research will be presented at the American Society for Pharmacology and Experimental Therapeutics (ASPET) Annual Meeting during Experimental Biology 2015.
Monteagudo’s research indicates a new possible chemotherapeutic target for treating GBM: transglutaminase 2 (TG2), a multifunctional protein that can regulate cell adhesion and motility. Given these documented functions of TG2, Monteagudo and her colleagues in the laboratory of Gail Johnson, Ph.D., at the University of Rochester, were interested in determining if TG2 played an important role in GBM cell growth. Based on previous research, Monteagudo and colleagues hypothesized that inhibition of TG2 would decrease GBM cell growth and survival. In order to test their hypothesis, they used primary GBM human-derived cells in the form of 3D spheres. The spheres retain the molecular integrity of the primary tumor to better mimic what is actually happening in the brain. Additionally, the study used two different established GBM cell lines to also look at proliferation using different techniques.
The researchers found that NC9, a novel drug specific for transglutaminases that was made by a collaborator, Jeffrey Keillor, Ph.D., at the University of Ottawa, effectively inhibited TG2 and decreased GBM cell growth and survival. These data indicate that TG2 is a possible chemotherapeutic target for GBM treatment.
The next step for this study will be to test the inhibitor in mice. The researchers will need to establish which route of administration will be more efficient for NC9’s delivery. Additionally, they need to recapitulate GBM in a mouse model to see if inhibition of TG2 will decrease tumor formation. Results from these studies will indicate the clinical impact of the research. Potentially this could offer a more specific and effective treatment for GBM patients.