Localization of shed human tumor gangliosides: association with serum lipoproteins.

Tumor gangliosides are biologically active (immunosuppressive and tumor-enhancing) cell surface molecules which are shed into the circulation in vivo. However, the mechanism of transport of these molecules (i.e., in solution or bound to proteins or other lipids) is not known. To resolve this question we traced, by direct chemical detection, the serum localization of a specific human tumor ganglioside, GD2, shed by neuroblastoma cells. Sera from patients with tumors were separated into the lipoprotein fractions [very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein] and lipoprotein-depleted serum. All three lipoprotein fractions contained GD2. 73% of the total GD2 was present in the LDL fraction, while very low-density lipoprotein and high-density lipoprotein contained 21 and 6%, respectively. Significantly, lipoprotein-depleted serum, which would contain both albumin-bound and free ganglioside, was devoid of GD2. Thus, shed neuroblastoma tumor gangliosides are exclusively associated with the serum lipoprotein (and predominantly LDL) fractions in vivo. These findings have implications for the immunological detection of these molecules and the development of approaches to their removal.