g(m3)-ganglioside and Astrocytoma

Limitations of classification schemes for brain tumors based solely on morphology have stimulated searches for molecular markers of nosologic and prognostic value. Gangliosides are logical candidates because there are high concentrations of them in the nervous system, there is evidence of their roles in regulation of growth and differentiation, and data from small series suggest correlations between ganglioside composition and glioma type.. Ganglioside compositions were determined for 70 primary human brain tumors: 16 low grade astrocytomas (LG), 12 anaplastic astrocytomas (AA), 34 glioblastoma multiformes (GBM), and 8 primitive neuroectodermal tumors (PNET). This method involved identification and quantitation of specific gangliosides using chemical analysis and immunoanalysis.. Among all tumor types, histologic grade correlated with a progressive loss of 1b gangliosides (P < 0.0001). GQ1b was higher in LGs than in AAs (P < 0.001). Both GT1b and GD1b were higher in AAs than GBMs (P < 0.01 and 0.05, respectively) and lower in PNETs than in GBMs (P < 0.05). GM3 was higher in PNETs than in any astrocytoma group and higher in GBMs than in either AAs or LGs. There was a significant difference in the content of 3'-LM1 among all groups (P < 0.005), between AAs and GBMs (P < 0.05), and between low grade ordinary and juvenile pilocytic astrocyomas (P < 0.01). The lacto-series ganglioside 3'-isoLM1 was present in all groups except PNET.. These results indicate that patterns of gangliosides could be of considerable value in refining the classification and diagnosis of primary human brain tumors.

Topics: Adult; Aged; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Female; G(M1) Ganglioside; G(M3) Ganglioside; Gangliosides; Glioblastoma; Humans; Male; Middle Aged; Nerve Growth Factors; Neuroectodermal Tumors, Primitive, Peripheral

After the observation that human mAb 32-27M reacts only with melanoma and astrocytoma cells cultured in the presence of fetal bovine serum, a novel pathway for the uptake of exogenous gangliosides, their further biosynthesis, and expression at the cell surface as novel Ag has been elucidated. The addition of fetal bovine serum to melanoma and astrocytoma cells growing in synthetic medium (insulin-transferrin-selenium) resulted in reactivity with Ab32-27M. As antibody 32-27M detects N-glycolylneuraminic acid (NeuGc)-containing gangliosides, the effect of adding a number of different gangliosides to melanoma and astrocytoma cells cultured in the synthetic medium was studied. Only the addition of NeuGc-GM3 resulted in the development of Ab32-27M reactivity. The identity of the antigenic structures developed after addition of fetal bovine serum or NeuGc-GM3 was determined by analysis of the gangliosides from both samples. The major component detected in melanoma cell lines was shown to be N-acetylneuraminic acid-NeuGc-GD3. Another, slower moving component, present in some melanomas and in astrocytomas may be N-acetylneuraminic acid-NeuGc-GD2. The cell type specificity for these processes can be most readily explained by postulating that all cells can take up exogenous gangliosides but only melanoma and astrocytoma cells have sufficiently high levels of GM3 alpha 2----8-sialyltransferase for the conversion of added NeuGc-GM3 to disialogangliosides to be effective. These results demonstrate a novel pathway for exogenous glycolipid processing that can lead to novel Ag expression but may also play a role in normal glycolipid metabolism and function.

Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Reactions; Antigens, Neoplasm; Antigens, Surface; Astrocytoma; Cattle; Cell Line; Cell-Free System; Epitopes; Fetal Blood; G(M3) Ganglioside; Gangliosides; Humans; Melanoma; Neuraminic Acids; Tumor Cells, Cultured

Many alterations of ganglioside content and distribution have been described in human and experimental tumours. Our previous data showed the presence of lipid alterations in meningiomas, in particular an increased monosialylganglioside content. Therefore we analyzed the distribution and content of gangliosides in various gliomas. The data show that ganglioside content is inversely proportional to tissue malignancy and that the ganglioside pattern can be described as lacking of polysialylgangliosides with increased GD3 content. The amount of GD3 (as percent of total gangliosides sialic acid) increases from 15% in astrocytomas grade I to 60% in grade IV. The GD3 increase seems to be almost specific of glioma. Because anti-GD3 antibodies could be used to localize immunohistochemically the ganglioside and to help the tumour grading, we used a purified preparation of GD3 to produce monoclonal antibodies in balb/c mice. But because some clones did produce anti-GD3 antibodies the low yield requires further experiments to obtain an antibody useful for this purpose.

Topics: Adult; Aged; Animals; Astrocytoma; Chromatography, Thin Layer; DNA, Neoplasm; G(M3) Ganglioside; Gangliosides; Glioblastoma; Humans; Mice; Mice, Inbred BALB C; Middle Aged

The serum concentration and composition of gangliosides were examined in 80 humans including 10 normal subjects. A significant increase was found in the total gangliosides of serum in 7 patients with cerebral astrocytomas. There was also an increased percentage of serum gangliosides with simpler structure, particularly GM3. The serum of patients with other intracranial tumors, including pituitary adenomas, ependymoma, teratoma, and metastases, did not show an increase in total ganglioside; however the pattern of simplification was found in these and in a few patients with extracranial tumors as well. The findings suggest that astrocytoma tumors shed sialoglycolipids into the circulation, and their assay may be useful in monitoring oncological therapy.

Topics: Astrocytoma; Brain Diseases; Brain Neoplasms; Chromatography, Thin Layer; G(M3) Ganglioside; Gangliosides; Humans; Neoplasms; Pons