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

• Published in: FEBS letters 2001-06, Vol.498 (1), p.116-120
• Main Authors: Ito, Akihiro, Handa, Kazuko, Withers, Donald A., Satoh, Makoto, Hakomori, Sen-itiroh
• Format: Article
• Language: English
• Subjects: 2→3 SnLc6, 2→3 sialylnorhexaosylceramide (VI3NeuAcnLc6); 2→3 SPG, 2→3 sialylparagloboside (IV3NeuAcnLc4); 2→6 SPG, 2→6 sialylparagloboside (IV6NeuAcnLc4); Adhesion; Animals; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Binding Sites; BSA, bovine serum albumin; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; COS Cells; Disease Progression; DSGG, disialogalactosylgloboside (V3NeuAcIV6NeuAcGb5); DSLc4, IV3NeuAcIII6NeuAcLc4; GalNAcDSLc4, IV4GalNAcIV3NeuAcIII6NeuAcLc4; Ganglioside; Gangliosides - metabolism; Gangliosides - physiology; Glycosphingolipids are abbreviated as recommended by IUPAC-IUB (J. Biol. Chem. 257 3347–3351, 262 13–18). Gangliosides are abbreviated according to Svennerholm (J. Lipid Res. 5 145–155); GSL, glycosphingolipid; Humans; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Lectins; Metastasis; MSGG, monosialogalactosylgloboside (V3NeuAcGb5); NK, natural killer; PBMC, peripheral blood mononuclear cells; PBS, 2.67 mM KCl, 1.47 mM K2HPO4, 138 mM NaCl, 8.1 mM Na2HPO4·7H2O; RCC, renal cell carcinoma; Renal cell carcinoma; siglec, sialic acid/immunoglobulin/lectin (Crocker et al., Glycobiology 8 v); Siglec7; SLe, sialyl-Lewis; SPG, sialylparagloboside; TLC, thin-layer chromatography; TOS-1 cell; Tumor Cells, Cultured
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(01)02476-0

Previous studies indicate that expression of higher gangliosides in renal cell carcinoma (RCC) is correlated with metastatic potential, particularly in the lung. Out of five major gangliosides in RCC, three disialogangliosides (disialogalactosylgloboside, IV 3NeuAcIII 6NeuAcLc 4, and IV 4GalNAcIV 3NeuAcIII 6NeuAcLc 4) bind strongly to siglec7, which is expressed highly in monocytes and natural killer cells. Out of other gangliosides tested, 2→6 sialylparagloboside, GD3, GD2, and GT1b, but not other lacto- or ganglio-series gangliosides, showed clear binding to siglec7. In view of preferential 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 expression of siglec7 in the lung. siglec7 is expressed highly in resident blood cells, but not in parenchymatous cells. TOS-1 cells aggregate together strongly through adhesion with peripheral blood mononuclear cells to form large clumps. This suggests the possibility that such aggregates may form embolisms of microvasculature, particularly in the lung, which initiate metastasis. Other possible roles of higher gangliosides in RCC in promoting metastasis and tumor progression are discussed.