Heidelberg - Scientists from the German Cancer Research Center () Heidelberg have identified an enzyme that is responsible for the dangerous stem cell properties in glioblastoma cells and at the same time could offer possible target for therapy. The work was published in the specialist journal Cell Stem Cell ().
If brain tumors return after therapy, this is due to cancer stem cells, which the treatment could not harm. "The only way to prevent glioblastoma from relapsing after treatment would be therapy that is effective against the brain tumor stem cells," explained Haikun Liu from the DKFZ.
But the problem is that brain tumors - Stem cells and the stem cells of the healthy brain shared many molecular features and properties. So far, there are no molecular target structures that are specific for cancer stem cells - so that the therapy does not damage healthy cells.
The scientists compared the protein structure of glioblastoma stem cells in mice with that of normal brain stem cells. Using RNA sequencing, they were able to quantify the quantities in which the cells produce individual proteins.
Among other things, they identified an enzyme of energy metabolism called glycerol-3-phosphate dehydrogenase 1 (GPD1), which is found in cancer stem cells, but not is formed in brain stem cells. Already about two weeks after the onset of cancer development, the researchers were able to detect GPD1 production in the growing tumor.
The researchers treated mice with the standard chemotherapeutic agent temozolomide and found: During the treatment, the GPD1-producing cells showed no division activity and remained in the sleep state that is characteristic of stem cells. But with the onset of relapse, they awoke. The scientists take this as strong indication that they are responsible for the recurrence of the tumor. If GPD1 was switched off in the tumor stem cells of the mice using genetic methods, the animals survived longer.
A database analysis of tumor genomes subsequently showed that in glioblastoma patients high GPD1 production with an unfavorable one Correlated prognosis. In other types of cancer, too, such as renal cell carcinoma, high GPD1 levels are associated with an unfavorable course.
Cell lines cultivated from human glioblastomas, whose GPD-1 the researchers had switched off, also no longer overgrew in the culture dish "Mini-tumors" approached - and thus lost typical stem cell ability.
"All of our results suggest that GPD1 is responsible for the stem cell properties of brain tumor stem cells.In normal brain stem cells, the enzyme does not seem to play particular role, ”says Haikun Liu, summarizing the researchers' results. You now want to check whether the enzyme is suitable as target structure for possible therapies.