Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression

Previous studies indicate that expression of higher gangliosides in renal c ell carcinoma (RCC) is correlated with metastatic potential, particularly i n the lung, Out of five major gangliosides in RCC, three disialoganglioside s (disialogalactosylgloboside, IV(3)NeuAcIII(6)NeuAcLc(4), and IV(4)Gal-NAc lV(3)NeuAcIII(6)NeuAcLc(4)) bind strongly to siglec7, which is expressed hi ghly in monocytes and natural killer cells. Out of other gangliosides teste d, 2 -->6 sialylparagloboside, GD3, GD2, and GT1b, but not other lacto- or ganglio-series gangliosides, showed clear binding to siglec7, In view of pr eferential metastasis of RCC to the lung, and binding of RCC cell line TOS- 1 to lung tissue sections as shown in our previous study, we examined expre ssion of siglec7 in the lung. siglec7 is expressed highly in resident blood cells, but not in parenchymatous cells. TOS-1 cells aggregate together str ongly through adhesion with peripheral blood mononuclear cells to form larg e clumps. This suggests the possibility that such aggregates may form embol isms of microvasculature, particularly in the lung, which initiate metastas is, Other possible roles of higher gangliosides in RCC in promoting metasta sis and tumor progression are discussed. (C) 2001 Published by Elsevier Sci ence B.V. on behalf of the Federation of European Biochemical Societies.