Surface expression of GD3 disialogangliosides 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 different metastatic potential and ganglioside expression were established from a single human melanoma cell line M4Be. Clones and variants derived from M4Be have been characterized at their surface by their gangliosides expression that were determined by flow cytometry with monoclonal antibodies. Gangliosides are membrane glycolipids containing sialic acid. Using an in vitro clonogenic assay and provided that cells were cultured for no more than 5 passages, variations in the cellular radiosensitivity of M4Be and of the 7 sublines were detected. This study shows that the lower the expression of GD3 disialoganglioside at the cell surface, both the higher their radiosensitivity in vitro and their metastatic potential in vivo. These results suggest that highly metastatic 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 ganglioside significantly increases their radioresistance in vitro and reduces their metastatic potential in vivo.
Thomas
C P
CP
Laboratoire de cancérologie expérimentale, INSERM U. 218, Lyon, France.
Buronfosse
A
A
Fertil
B
B
Portoukalian
J
J
D002462:Cell Membrane / Q000378:metabolism*; D002999:Clone Cells / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure
D005732:Gangliosides; C025447:sialogangliosides