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Decreased Accessibility of Globotriaosylceramide Associated with Decreased Tumorigenicity in Burkitt's Lymphoma Variants Induced by Immunoselection¹

Laboratoire de Pharmacologie Moléculaire (URA 158 CNRS, U 140 INSERM) [S. J., A. K. L., P. W., J-B. L.] and Groupe d'Immunologie des Tumeurs (UA 1156 CNRS) [J. W.], Institut Gustave-Roussy, Rue Camille Desmoulins, 94805 Villejuif, and Laboratoire de Cytométrie (UA 47 CNRS) [Z. M.], Villejuif, France

To investigate a role for globotriaosylceramide (Gb₃) as a tumor-associated antigen, variant cells resistant to treatment with complement and monoclonal antibody 38–13, which recognizes Gb₃, were selected from a Burkitt's lymphoma cell line, Ramos. Variant cells displayed a clear decrease of antibody-binding capacity whereas the amount of Gb₃ at their plasma membrane was not significantly different from that of Ramos parental cells. This demonstrated a reduced accessibility of Gb₃ at the surface of variant cells. In parallel, no changes in other surface antigens were recorded as compared to those in Ramos cells. No changes of proliferative properties in suspension culture or of c-myc expression were observed although variant cells showed a decreased colony-forming capacity in agar. Variant cells showed a significant reduction in tumorigenic potential when injected s.c. into nude mice. The decreased tumorigenicity appeared related to the low antibody-binding capacity because both tumorigenicity and Gb₃ antigenicity were recovered in parallel in revertant cells growing in suspension culture. In vivo, after two transplantations of variant cells into mice, cells isolated from the few induced tumors still retained the low antibody-binding capacity.

¹ Part of this work was presented at the 79th Annual Meeting of the American Association for Cancer Research, New Orleans, May 1988 (35). This work was supported by grants from Centre National pour la Recherche Scientifique, INSERM, Association pour la Recherche sur le Cancer, Fondation pour la Recherche Médicale and Université Pierre et Marie Curie.

² To whom requests for reprints should be addressed.

Received 9/30/88. Revised 7/28/89. Accepted 9/ 5/89.