A novel ganglioside isolated from renal cell carcinoma

In renal cell carcinoma (RCC), the level of higher gangliosides is correlat ed with degree of metastatic potential, and cell lines derived from metasta tic deposits of RCC are characterized by high expression of disialoganglios ides (Saito, S,, Orikasa, S., Ohyama, C., Satoh, M,, and Fukushi, Y. (1991) Int. J. Cancer 49, 329-334 and Saito, S., Orikasa, S., Satoh, M., Ohyama, C., Ito, A., and Takahashi, T, (1997) Jpn. J. Cancer Res. (Gann) 88, 652-65 9). We now report two disialogangliosides, G1 and G2, found in the RCC cell line TOS-1, G1 from TOS-1 cells was characterized as having a novel hybrid structure between ganglio-series (region I as in Structure I; same as the terminal structure of ganglioside GM2), and the lacto-series type 1 (region II). The characterization was based on reactivity with various monoclonal antibodies (mAbs) with defined epitope specificity, as well as monosacchari de and fatty acid component analysis, H-1 NMR spectroscopy, and electrospra y ionization mass spectrometry of the intact compound. G1 showed strong rea ctivity with mAb RM2, raised originally against TOS-1 cells, and weak cross -reactivity with anti-GM2 mAb MK-1-8. The antigen is hereby termed GalNAc d isialosyl Lc(4)Cer (IV(4)GalNAcIV(3)NeuAcIII(6)NeuAcLc(4); abbreviated GalN AcDSLc(4)). [GRAPHICS] G2 was identified by H-1 NMR and mass spectrometry as having a structure si milar to Structure I but without the GalNAc beta1 -->4 substitution and sho wed strong reactivity with mAb FH9 reported previously to be specific for d isialosyl lacto-series type 1 (disialosyl Lc(4)) having vicinal alpha2 -->3 and alpha2 -->6 sialosyl residues, an antigen associated with human coloni c cancer. Clinicopathological studies indicate that expression of these dis ialoganglioside antigems in RCC tissue is correlated with the metastatic po tential of RCC.