Thomas C P, Buronfosse A, Fertil B, Portoukalian J
Laboratoire de cancérologie expérimentale, INSERM U. 218, Lyon, France.
C R Acad Sci III. 1995 Dec;318(12):1233-8.
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.
利用本实验室建立的黑色素瘤自发性肺转移实验模型，从单一的人黑色素瘤细胞系M4Be中建立了7个具有不同转移潜能和神经节苷脂表达的亚系（变体和克隆）。通过用单克隆抗体进行流式细胞术测定其神经节苷脂表达，对源自M4Be的克隆和变体进行了表面特征分析。神经节苷脂是含有唾液酸的膜糖脂。使用体外克隆形成试验，并且前提是细胞培养不超过5代，检测到了M4Be和7个亚系细胞放射敏感性的变化。这项研究表明，细胞表面GD3二唾液酸神经节苷脂的表达越低，其体外放射敏感性和体内转移潜能就越高。这些结果表明，高转移性人黑色素瘤细胞对放射敏感且表面神经节苷脂缺乏。这一假设的强化来自于实验，实验表明用外源性神经节苷脂孵育放射敏感细胞可显著提高其体外放射抗性并降低其体内转移潜能。
