Gabri Mariano R, Ripoll Giselle V, Alonso Daniel F, Gómez Daniel E
Laboratory of Molecular Oncology, Department of Science and Technology, Quilmes National University, Bernal B1876BXD, Buenos Aires, Argentina.
J Cancer Res Clin Oncol. 2002 Dec;128(12):669-77. doi: 10.1007/s00432-002-0385-7. Epub 2002 Nov 14.
To examine the role of GM3 monosialoganglioside and sialic acid in the antitumor activity of a vaccine based on GM3, hydrophobically conjugated with the outer-membrane-protein complex from Neisseria meningitidis (GM3/VSSP).
In order to evaluate the relationship between antitumor activity and the presence of GM3 on the surface of tumor cells, we used two murine tumor cell lines with different ganglioside expression. Syngeneic mice were immunized with four i.m. doses of GM3/VSSP (120 micro g) at 14-day intervals and challenged subcutaneously with tumor cells.
B16 melanoma cells showed GM3 on cell surface and GM3-dependent in vitro growth. As expected, preimmunization with the vaccine significantly inhibited tumor formation and prolonged survival in mice challenged with B16 cells. In contrast, no antitumor effect was observed in mice challenged with GM3-negative F3II mammary carcinoma cells. The reactivity of sera from immunized mice against B16 cells was confirmed by flow cytometry and immunoperoxidase staining. Depletion of sialic acid residues from the cell surface completely abolished antibody response against melanoma cells.
These results indicate that the antitumor activity of GM3/VSSP is associated with GM3 expression on tumor cell surface and demonstrate a major role of sialic acid in the humoral response of vaccinated mice.
研究GM3单唾液酸神经节苷脂和唾液酸在基于GM3的疫苗抗肿瘤活性中的作用，该疫苗与脑膜炎奈瑟菌外膜蛋白复合物（GM3/VSSP）疏水共轭。
为了评估抗肿瘤活性与肿瘤细胞表面GM3存在之间的关系，我们使用了两种神经节苷脂表达不同的小鼠肿瘤细胞系。同基因小鼠每隔14天肌肉注射4剂GM3/VSSP（120微克）进行免疫，并皮下接种肿瘤细胞进行攻击。
B16黑色素瘤细胞在细胞表面显示GM3且具有GM3依赖性体外生长。正如预期的那样，用疫苗进行预免疫可显著抑制接种B16细胞的小鼠的肿瘤形成并延长其生存期。相比之下，接种GM3阴性的F3II乳腺癌细胞的小鼠未观察到抗肿瘤作用。通过流式细胞术和免疫过氧化物酶染色证实了免疫小鼠血清对B16细胞的反应性。细胞表面唾液酸残基的去除完全消除了针对黑色素瘤细胞的抗体反应。
这些结果表明GM3/VSSP的抗肿瘤活性与肿瘤细胞表面的GM3表达相关，并证明了唾液酸在接种疫苗小鼠的体液反应中的主要作用。
