Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression (vol 498, pg116, 2001)

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)GalNAcI V(3)NeuAcIII(6)NeuAcLc(4)) bind strongly to siglec7, which is expressed hig hly in monocytes and natural killer cells. Out of other gangliosides tested , 2 -->6 sialylparagloboside, GD3, GD2, and GT1b, but not other lacto- or g anglio-series gangliosides, showed clear binding to siglec7. In view of pre ferential 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 expres sion of siglec7 in the lung. siglec7 is expressed highly in resident blood cells, but not in parenchymatous cells. TOS-1 cells aggregate together stro ngly through adhesion with peripheral blood mononuclear cells to form large clumps. This suggests the possibility that such aggregates may form emboli sms of microvasculature, particularly in the lung, which initiate metastasi s. Other possible roles of higher gangliosides in RCC in promoting metastas is and tumor progression are discussed. (C) 2001 Federation of European Bio chemical Societies. Published by Elsevier Science B.V. All rights reserved.