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Localization of Shed Human Tumor Gangliosides: Association with Serum Lipoproteins¹

Division of Hematology/Oncology, Department of Pediatrics, UCLA School of Medicine, Los Angeles, California [L. V., S. L.]; Bone Marrow Transplantation Center, Rush Medical College, Chicago, IL [L. V.]; and Center for Cancer and Transplantation Biology, Children's National Medical Center, Washington, D.C. [S. L.]

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., is 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, G_D2, 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 G_D2. 73% of the total G_D2 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 G_D2. 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.

¹ This work was supported by Grant CA 42361 from the National Cancer Institute, PDT-270B from the American Cancer Society, Concern and Concern II Foundations, and by the Phi Beta Psi Sorority.

² To whom requests for reprints should be addressed, at (present address): Center for Cancer and Transplantation Biology, Children's National Medical Center, Washington, D.C. 20010.

Received 9/20/91. Accepted 12/ 2/91.

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