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内容記述 |
In renal cell carcinoma (RCC), the level of higher gangliosides is correlated with degree of metastatic potential, and cell lines derived from metastatic deposits of RCC are characterized by high expression of disialogangliosides (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, 652–659). 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 FTI; 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 monosaccharide and fatty acid component analysis, ^1H NMR spectroscopy, and electrospray ionization mass spectrometry of the intact compound. G1 showed strong reactivity 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 disialosyl Lc_4Cer (IV^4GalNAcIV^3NeuAcIII^6NeuAcLc_4; abbreviated GalNAcDSLc_4). G2 was identified by^1H NMR and mass spectrometry as having a structure similar to Structure FTI but without the GalNAcβ1→4 substitution and showed strong reactivity with mAb FH9 reported previously to be specific for disialosyl lacto-series type 1 (disialosyl Lc_4) having vicinal α2→3 and α2→6 sialosyl residues, an antigen associated with human colonic cancer. Clinicopathological studies indicate that expression of these disialoganglioside antigens in RCC tissue is correlated with the metastatic potential of RCC. |