SURFACE EXPRESSION OF GD3 DISIALOGANGLIOS IDES IN HUMAN-MELANOMA CELLS IS CORRELATED TO BOTH METASTATIC POTENTIAL IN-VIVO AND RADIOSENSITIVITY IN-VITRO

With an experimental model of spontaneous lung metastases of melanoma developed in this laboratory, 7 sublines (variants and clones) with di fferent metastatic potential and ganglioside expression were establish ed from a single human melanoma cell line M4Be. Clones and variants de rived from M4Be have been characterized at their surface by their gang liosides expression that were determined by flow cytometry with monocl onal antibodies. Gangliosides are membrane glycolipids containing sial ic acid. Using an in vitro clongenic assay and provided that cells wer e cultured for no more than 5 passages, variations in the cellular rad iosensitivity of M4Be and of the 7 sublines were detected. This study shows that the lower the expression of GD3 disialoganglioside at the c ell surface, both the higher their radiosensitivity in vitro and their metastatic potential in vivo. These results suggest that highly metas tatic human melanoma cells are radiosensitive and deficient in surface gangliosides. Strengthening of this hypothesis arise from experiments showing that the incubation of radiosensitive cells with exogenous ga nglioside significantly increases their radioresistance in vitro and r educes their metastatic potential in vivo.