Human melanoma cell invasion is inhibited in vitro by swainsonine and deoxymannojirimycin with a concomitant decrease in collagenase IV expression.
Human melanoma cell invasion is inhibited in vitro by swainsonine and deoxymannojirimycin with a concomitant decrease in collagenase IV expression.
复制标题
苦马豆素和脱氧甘露尻霉素在体外抑制人黑色素瘤细胞侵袭，同时降低胶原酶 IV 表达。
DOI：
10.1097/00008390-199104000-00006
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发表时间：
1991
影响因子：
2.2
通讯作者：
Hendrix,MJ
中科院分区：
文献类型：
--
作者：
Seftor,RE;Seftor,EA;Grimes,WJ;Liotta,LA;Stetler-Stevenson,WG;Welch,DR;Hendrix,MJ
用苦马豆素(高尔基体α-甘露糖苷酶II的抑制剂)或脱氧甘露糖苷酶(高尔基体α-甘露糖苷酶I的抑制剂)处理两株恶性和侵袭性人黑色素瘤细胞48h后，细胞体外侵袭重组基底膜的能力呈剂量依赖性下降。这种作用在药物撤除后48小时内可逆。两种药物均使两株细胞对凝集素、白血球凝集素(PHA-L)的细胞毒作用产生更强的抵抗力，对凝集素刀豆蛋白A更敏感，这间接表明细胞表面寡糖组成和结构发生了变化，这与这些药物对N-连接低聚糖加工的已知作用一致。经处理的细胞与重组基底膜或人脐静脉内皮细胞单层的粘附率降低了25%-33%，而细胞的增殖率没有变化。而停药后48h内恢复正常的人IV型胶原酶基因表达水平则明显下降。这些结果表明，药物引起的细胞表面低聚糖组成和结构的改变，伴随着IV型胶原酶的mRNA和分泌水平的下降，以及这些细胞的侵袭能力之间存在相关性。
A 48 h pretreatment of two malignant and invasive human melanoma cell lines with either swainsonine (an inhibitor of Golgi alpha-mannosidase II) or deoxymannojirimycin (a Golgi alpha-mannosidase I inhibitor) resulted in a dose-dependent decrease in the cells' ability to invade a reconstituted basement membrane in vitro. This effect was reversible within 48 h of removing the drugs. Treatment with either drug resulted in both cell lines being more resistant to the cytotoxic effects of the lectin leukoagglutinin (PHA-L) and more sensitive to the lectin concanavalin A which indirectly indicated a change in the cell surface oligosaccharide composition and structure consistent with the known effects of these drugs on N-linked oligosaccharide processing. A 25–33% decrease was noted in the adhesion of treated cells to either a reconstituted basement membrane or human umbilical vein endothelial cell monolayer while no change was measured in the cells' proliferative rates. A correlative decrease was observed, however, in the expression of human type IV collagenase mRNA which was recovered within 48 h of removing the drugs. These results suggest that a correlation exists between the drug-induced changes in the cell surface oligosaccharide composition and structure with a concomitant decrease in the mRNA and secreted levels of type IV collagenase and the ability of these cells to invade.