gms | German Medical Science

Objective: Death receptor 6 (DR6), a member of the tumor necrosis factor superfamily, is known to play a role in different kind of tumors like adult sarcoma, prostate- and breast cancer. DR6 is also crucial in neuronal destruction in neurodegenerative disease such as amyotrophic lateral sclerosis. This study investigates the expression pattern of DR6 in glioma and the effect of temozolomide on its expression to assess possible treatment-options for DR6-antagonists.

Methods: The expression level of DR6 was measured by using Western Blot in 38 different samples, sorted relative to their grade and therapy (control, grade II, grade III, IDH mutant Glioblastoma, IDH wildtype Glioblastoma, IDH mutant Glioblastoma treated with temozolomide, IDH wildtype Glioblastoma treated with temozolomide). All samples were incubated with a rabbit polyclonal antibody against DR6. A proper secondary peroxidase-conjugated antibody was utilized for visualization. To normalize the results, ß-actin antibody was used.

Results: The expression of DR6 was upregulated in glioma compared to non-tumorous tissue (glioma: 0.47 ± 0.52 vs. control: 0.24 ± 0.16). Moreover, a higher expression with increasing malignancy of the tumor is shown in our data (grade II: 0.38 ± 0.26; grade III: 0.48 ± 0.28 ; GBM: 0.7 ± 0.9). DR6 did not differ from IDH-mutant to wildtype GBM (GBM IDH-mutant: 0.67 ± 0.6; GBM wildtype: 0.73 ± 1.22).

A trend towards a decreased expression of DR6 in the recurrent situation after treatment with temozolomide was visible (GBM IDH-mutant: 0.67 ± 0.6; GBM IDH-mutant + TMZ: 0.34 ± 0.35; GBM IDH-wildtype: 0.73 ± 1.2; GBM wildtype + TMZ: 0.17 ± 0.14).

Conclusion: High-grade gliomas show higher levels of DR6. Furthermore, temozolomide seems to suppress the expression of death receptor 6, which has to be taken into account for the evaluation of DR6 antagonists in glioma.