Ganglioside, disialosyl globopentaosylceramide (DSGB5), enhances the migration of renal cell carcinoma cells

Abstract

About one third of renal cell carcinoma (RCC) patients exhibit metastasis upon initial presentation. However, the molecular basis for RCC metastasis is not fully understood. A ganglioside, disialosyl globopentaosylceramide (DSGb5), was originally isolated from RCC tissue extracts, and its expression is correlated with RCC metastatic potential. DSGb5 is synthesized by GalNAc α2,6-sialyltransferase VI (ST6GalNAcVI) and is expressed on the surface of RCC cells. Importantly, DSGb5 binds to sialic acid-binding Ig-like lectin-7 (Siglec-7) expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity. However, the role of DSGb5 in RCC progression remains obscure. To address this issue, we used ACHN cells derived from malignant pleural effusion of a patient with metastatic RCC. Using the limiting dilution method, we isolated three independent clones with different DSGb5 expression levels. Comparison of these clones indicated that the cloned cells with high DSGb5 expression levels exhibited greater migration potential, compared to the clone with low DSGb5 expression levels. In contrast, DSGb5 expression levels exerted no signifcant effect on cell proliferation. We then established the ACHN-derived cell lines that stably expressed siRNA against ST6GalNAcVI mRNA or control siRNA. Importantly, the ST6GalNAcVI-knockdown cells expressed low levels of DSGb5. We thus demonstrated the signifcantly decreased migration potential of the ST6GalNAcVI-knockdown cells with low DSGb5 expression levels, compared to the control siRNA-transfected cells expressing high DSGb5 levels, but no signifcant difference in the cell proliferation. Thus, DSGb5 expression may ensure the migration of RCC cells. We propose that DSGb5 expressed on RCC cells may determine their metastatic capability.