Cancer Cell paper found that in brain cancer, when CD95L activates CD95, a process that usually triggers cancer cell death, a protein that promotes the disease was produced.
The apoptotsis-inducing protein CD95 was previously thought to be a target initiating cell death in cancer through activation by the binding of its partner, CD95L. Researchers discovered, however, that activation of CD95 actually induces glioblastoma’s migration into brain tissue.
In the study, the scientists found that there were large amounts of CD95 in glioblastoma cells while CD95L was localized primarily to invasive front, the border between tumor tissue and healthy brain tissue. Despite the presence of both molecules, the investigators say that the cells were still resistant to apoptosis.
The team also found that if CD95 on the surface of glioblastoma cells is activated by CD95L, it leads to the production of a protein called MMP9, which is known to be a molecular scissors. MMP9 cuts through the network of protein fibers that separate different tissue layers of the body. With the aid of these protein scissors, tumor cells invade healthy tissue and form the protrusions that penetrate brain tissue.
The scientists also found that if they treated mice that had been transplanted with glioblastoma with an antibody that blocks CD95, the migration of cancer cells ceded.
“This is almost a paradigm shift,” says Ana Martin-Villalba, M.D., Ph.D., one of the authors and an investigator at the German Cancer Research Center. “Up to now, the goal has been to promote formation of CD95 and CD95L in tumor cells. In the case of glioblastoma, we now have to warn against this approach: This would only additionally support the spread of the tumor. The goal is rather to block activation of CD95.”
The study was conducted by researchers at the German Cancer Research Center, Apogenix, University of Heidelberg, and University of Mannheim. Findings were published in the March 11 issue of Cancer Cell.
