Incorporation, remodeling and re-expression of exogenous gangliosides in human cancer cell lines in vitro and in vivo.
Human neuroblastomas and gliomas express high levels of GD2 ganglioside. Mechanisms for the re-expression of GD2 after the incorporation of an exogenous precursor structure were analyzed using a human heterophilic monoclonal antibody (mAb) together with mouse anti-GD3 and mouse anti-GD2 mAbs. First, mouse anti-GD2 mAb 220-51 was generated and its reactivity was confirmed to be almost identical with that of the well-known mAb 3F8 antibody. As reported previously for GD3 variants, new ganglioside antigens reactive with human mAb 32-27 were analyzed by culturing an astrocytoma cell line AS in the presence of NeuGc-GM3. Analysis of the extracted gangliosides from AS thus cultured revealed a new component detected with mAb 32-27, migrating similarly to GD2. Incorporated NeuGc-GM3 seemed to be converted to NeuAc-NeuGc-type GD3, and then to NeuAc-NeuGc-type GD2 with alpha2,8-sialyltransferase and beta1,4-GalNAc transferase, respectively. In addition, AS was inoculated into nude mice, and glycolipids were extracted from generated tumors. Analysis of the ganglioside components using mAbs indicated that NeuAc-NeuGc-type GD2 was generated in the xenogeneic tumors by incorporating NeuGc-GM3 from mouse blood. These results indicated the presence of a pathway for utilization of exogenous gangliosides for remodeling and re-expression in vivo.
Department of Biochemistry II, Nagoya University School of Medicine, Nagoya 466-0065, Japan.
Masashi
M
Nishio
Koichi
K
Furukawa
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001254:Astrocytoma / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D002855:Chromatography, Thin Layer; D005434:Flow Cytometry; D005732:Gangliosides / Q000096:biosynthesis*; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008954:Models, Biological; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009368:Neoplasm Transplantation; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D005732:Gangliosides; C026226:ganglioside, GD3; C019403:ganglioside, GD2; D016695:Glycosyltransferases; D019158:N-Acetylneuraminic Acid