DETECTION OF MEDULLOBLASTOMA AND ASTROCYTOMA-ASSOCIATED GANGLIOSIDE C-D3 IN CEREBROSPINAL-FLUID

Shedding of gangliosides by tumor cells may enhance tumor development. We recently showed that cells of the human brain tumor, medulloblasto ma, shed gangliosides in vitro and have therefore examined ganglioside shedding by pediatric brain tumors into the cerebrospinal fluid (CSF) . G(D3), a major ganglioside in medulloblastoma and astrocytoma, was t he target for detection in the CSF by immunostaining using the monoclo nal antibody R24 and enhanced chemiluminescence detection. Mean CSF G( D3) levels in patients with medulloblastomas (n = 9) and astrocytomas (n = 10) were significantly higher than those of controls (mean +/- SD 44.7 +/- 8.4 versus 18.2 +/- 1.9 pmol/ml, n = 20, P < 0.0002). Mass s pectrometric analysis showed that tumor-derived ganglioside G(D3) cont ained heterogeneous ceramide structures and, interestingly, the cerami de subspecies with shorter fatty acyl chains were selectively shed. Th e elevated CSF G(D3) concentrations in patients with medulloblastoma a nd astrocytoma support the concept that ganglioside shedding, which ma y have significant biological consequences, is characteristic of human brain tumors. (C) 1997 Elsevier Science Ireland Ltd.