Tardif M, Coulombe J, Soulières D, Rousseau A P, Pelletier G
Centre de Recherche en Rhumatologie et Immunologie, Sainte-Foy, Québec, Canada.
Int J Cancer. 1996 Sep 27;68(1):97-101. doi: 10.1002/(SICI)1097-0215(19960927)68:1<97::AID-IJC17>3.0.CO;2-3.
The inability of current therapy to prevent metastases arising from uveal melanoma often results in patient mortality. With the goal of developing a treatment for metastasis, gangliosides were studied as potential tumor-associated antigens. Our report describes the production of a metastatic liver variant (MH) from a human uveal melanoma cell line (SP6.5). Cells were injected into nude mouse spleens and liver metastases collected 2 months later. After 21 days of in vitro subculture, the cells were re-injected into normal nude mice spleen; 10 cycles (MH10) were performed. Gangliosides were extracted, purified, chromatographed on HPTLC plates and sprayed with a resorcinol-HCl reagent, the sialic acid spots being quantified by densitometry. Gangliosides were analyzed in each metastatic liver variant and compared with the SP6.5 s.c. tumor. The results showed a significant increase in GM3 and a significant decrease in GD3 and GD2 in the last metastatic variants obtained (MH5, MH8, MH9 and MH1O) compared with the primary s.c. tumor, SP6.5. Such evolution in the ganglioside pattern was maintained throughout the progression of the different liver variants. Our results indicate that precursor ganglioside GM3 and gangliosides GD3 and GD2 could be associated with neoplastic evolution of malignancy of human uveal melanoma in nude mice.
目前的治疗方法无法预防葡萄膜黑色素瘤转移，这常常导致患者死亡。为了开发一种治疗转移的方法，神经节苷脂作为潜在的肿瘤相关抗原进行了研究。我们的报告描述了从人葡萄膜黑色素瘤细胞系（SP6.5）产生转移性肝变体（MH）的过程。将细胞注射到裸鼠脾脏中，2个月后收集肝转移灶。体外传代培养21天后，将细胞重新注射到正常裸鼠脾脏中；进行了10个周期（MH10）。提取、纯化神经节苷脂，在高效薄层层析板上进行色谱分析，并用间苯二酚-盐酸试剂喷雾，通过光密度法对唾液酸斑点进行定量。分析每个转移性肝变体中的神经节苷脂，并与皮下肿瘤SP6.5进行比较。结果显示，与原发性皮下肿瘤SP6.5相比，在最后获得的转移性变体（MH5、MH8、MH9和MH10）中，GM3显著增加，GD3和GD2显著减少。在不同肝变体的进展过程中，神经节苷脂模式的这种演变一直保持。我们的结果表明，神经节苷脂前体GM3以及神经节苷脂GD3和GD2可能与人葡萄膜黑色素瘤在裸鼠中的恶性肿瘤演变有关。
