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.