Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas

Glial cell line-derived neurotrophic factor (GDNF), a sequence-related fact or of the transforming growth factor-P family, has been identified as a pot ent neurotrophic factor for a variety of neuronal cell populations. At pres ent, it is still unknown whether human gliomas in vivo are also capable of producing GDNF. We studied the expression of GDNF in 14 human glioblastomas , 1 gliosarcoma and 5 astrocytomas. Using an enzyme-linked immunosorbent as say, the amount of GDNF was quantified in human gliomas and compared to GDN F-expression in C6 glioma cells, mouse fibroblasts and normal human and rat brain. Mean concentration of GDNF in gliomas was 937 +/- 140 pg GDNF/g tis sue (n = 20). C6 cells revealed the highest expression levels of 2,837 +/- 813 pg/g, whereas mouse 3T3 fibroblasts showed no detectable GDNF protein. Mean GDNF tissue levels in normal human and rat brain were significantly lo wer. Using reverse transcriptase-polymerase chain reaction, GDNF mRNA was d etected in human gliomas and in rat C6 cells. Immunohistochemistry revealed strong GDNF- and GDNF receptor-alpha 1-expressing tumor cells in human gli oma tissue. These results show that glial tumors, even in the most dediffer entiated form of glioblastoma, express GDNF at concentrations up to five ti mes higher compared to normal human brain. This overexpression of GDNF may be of biological relevance for proliferation of glial tumors in humans.