Humphries M J, Matsumoto K, White S L, Olden K
Proc Natl Acad Sci U S A. 1986 Mar;83(6):1752-6. doi: 10.1073/pnas.83.6.1752.
Oligosaccharide moieties of cell-surface glycoconjugates are thought to be involved in recognition events associated with tumor metastasis and invasion. Using swainsonine (SW), an inhibitor of Golgi alpha-mannosidase II that results in the formation of hybrid-type oligosaccharides on N-linked glycoproteins, we have tested the hypothesis that specific glycan structures are required for pulmonary colonization by tumor cells. B16-F10 murine melanoma cells were treated with SW in growth medium and then injected intravenously into syngeneic C57BL/6 mice. This treatment resulted in dramatic inhibition of colonization, but it had no effect on B16-F10 viability or on cellular tumorigenicity after subcutaneous implantation. SW-treated radiolabeled B16-F10 cells were cleared from the lungs at a greater rate than control cells, suggesting that one effect of treatment is to alter tumor cell retention in the target organ. Our results implicate specific glycan structures in pulmonary colonization and offer a potential approach for identification of specific macromolecules involved in tumor cell-organ recognition during metastasis.
细胞表面糖缀合物的寡糖部分被认为参与了与肿瘤转移和侵袭相关的识别过程。我们使用了苦马豆素(SW),一种高尔基体α-甘露糖苷酶II的抑制剂,它会导致N-连接糖蛋白上形成杂合型寡糖,来检验肿瘤细胞在肺部定植需要特定聚糖结构这一假说。将生长培养基中的B16-F10小鼠黑色素瘤细胞用SW处理,然后静脉注射到同基因的C57BL/6小鼠体内。这种处理导致定植受到显著抑制,但对B16-F10细胞的活力或皮下植入后的细胞致瘤性没有影响。与对照细胞相比,经SW处理的放射性标记B16-F10细胞从肺部清除的速率更快,这表明处理的一个作用是改变肿瘤细胞在靶器官中的滞留情况。我们的结果表明特定聚糖结构与肺部定植有关,并为识别转移过程中参与肿瘤细胞-器官识别的特定大分子提供了一种潜在方法。