DISIALOSYL GALACTOSYLGLOBOSIDE AS AN ADHESION MOLECULE EXPRESSED ON RENAL-CELL CARCINOMA AND ITS RELATIONSHIP TO METASTATIC POTENTIAL

Aberrant glycosylation expressed in specific types of human cancer may define stage, direction, and fate of tumor progression, Well-studied examples are expression of sialosyl-lewis(x) or sialosyl-lewis(a) in c olorectal carcinoma and histo-blood group A and H/Le(y) in lung cancer , In renal cell carcinoma (RCC), expression of sialosyl-lewis(x) has n o correlation with metastatic potential, Clinicopathological studies h ave revealed that the degree of expression of disialosyl galactosylglo boside (DSGG) and monosialosyl galactosylgloboside is correlated with metastatic potential (to lung and lymph nodes) of RCC and inversely co rrelated with patient survival, In the present study, we compared the adhesion of RCC lines to sections of various tissues measured by Stamp er-Woodruff assay and other similar assays under dynamic flow conditio ns, Of the eight RCC lines tested, only TOS-1 (which expresses DSGG) b ound strongly to lung tissue sections, TOS-1 did not bind to sections of liver, kidney, or lymph nodes, In the same eight RCC lines, me also compared expression of DSGG and monosialosyl galactosylgloboside (ref lected by reactivity with RM1 and RM2), overall ganglioside patterns, and correlation with lung tissue-binding ability, Under both static an d dynamic flow conditions, the binding of TOS-1 cells to lung alveolar tissue was correlated with their DSGG expression, i.e., the binding w as inhibited by RM2 but not by RM1. This binding was also inhibited by sialidase but not by EDTA (i.e., it was CA(2+) independent), The othe r seven cell lines (TOS-2, TOS-M, SMKT-R1, -R2, -R3, and -R4, and ACHN ), which do not express DSGG, showed much weaker adhesion to lung tiss ue, None of the eight cell lines showed E- or P-selectin-dependent adh esion. These results suggest the existence of a yet-uncharacterized si aloadhesive receptor that specifically recognizes DSGG, This receptor could be the binding target in RCC metastasis to lung.