[Human glioma malignancy grade and migratory capacity depending on expression of GDNF isoforms in vitro].

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is essential in maintaining the viability, function and differentiation of neuronal cells. In addition to its function in healthy nervous tissue, GDNF is involved in pathological processes, such as glioma growth. GDNF is represented by 2 main isoforms: pre-α-pro-GDNF (αGDNF) and pre-β-pro-GDNF (βGDNF). αGDNF maintains cell viability, and βGDNF has neurotrophic properties. The relationship between GDNF expression and human glioma malignancy grade, as well as migratory properties of tumor cells remains poorly understood.

Objective: To assess the expression of mRNA splice variants of GDNF in glioma cell cultures with various malignancy grades (I-IV) and degrees of migration.

Material and methods: In this study, αGDNF and βGDNF expression was analyzed in 15 human glioma cell cultures using Southern blot hybridization of GDNF cDNA and reverse transcription with PCR to amplify splice variants of GDNF mRNA.

Results: The highest expression of αGDNF and βGDNF isoforms was observed in cell cultures of human gliomas with extensive migratory activity. Low βGDNF expression without αGDNF expression is typical only for gliomas with low migratory activity. In addition, we found additional patterns of mRNA expression that have not been previously described.

Conclusion: The relationship between GDNF and malignancy grade is unclear. Nevertheless, GDNF expression is higher in glioblastomas. Overall GDNF expression is increased in glioma cells with high migration activity. At the same time, αGDNF and βGDNF isoforms demonstrate higher expression in actively migrating cells that can indicate their participation in regulation of tumor migration properties. No αGDNF expression with simultaneous low βGDNF expression may be a prognostic sign of low migration activity of human glioma cells.