Enhanced GM3 expression, associated with decreased invasiveness, is induced by brefeldin A in bladder cancer cells.
Enhanced GM3 expression, associated with decreased invasiveness, is induced by brefeldin A in bladder cancer cells.
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DOI：
10.3892/ijo.19.4.723
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发表时间：
2001-10
影响因子：
5.2
通讯作者：
M. Satoh;A. Ito;H. Nojiri;K. Handa;K. Numahata;C. Ohyama;S. Saito;S. Hoshi;S. Hakomori
中科院分区：
文献类型：
--
作者：
M. Satoh;A. Ito;H. Nojiri;K. Handa;K. Numahata;C. Ohyama;S. Saito;S. Hoshi;S. Hakomori
我们之前报道过，非侵袭性膀胱癌表达高水平的 GM3 神经节苷脂，而侵袭性肿瘤表达低水平。由于从真菌中分离出的大环内酯布雷菲德菌素 A (BFA) 极大地改变了高尔基体中的鞘糖脂合成，因此我们研究了 BFA 对鞘糖脂表达和膀胱癌细胞系侵袭性的影响。在 BFA 治疗后，只有侵袭性肿瘤中的 GM3 合成大大增强；在侵袭性和非侵袭性肿瘤中，其他具有乳系列2型或球系列结构的鞘糖脂的合成没有改变。膀胱癌细胞的侵袭力大大降低，这与 BFA 治疗诱导的 GM3 合成的大幅增加有关。 BFA 处理后，侵袭性细胞系 YTS1 中唾液酸-Lex 的表达水平没有变化，该水平为细胞提供了对 E-选择素的粘附特性。所有膀胱癌细胞系，无论侵袭性如何，都高度表达四跨膜蛋白 CD9。 GM3 被认为是 CD9 控制肿瘤细胞运动的辅助因子。 CD9 的下调与肿瘤细胞的转移特性和结肠癌患者的生存有关。因此，BFA 诱导的 GM3 合成增强，导致膀胱癌侵袭性降低，这归因于 GM3 将整合素与 CD9 互连的能力，类似于结肠癌和许多其他类型的癌症。
We reported previously that non-invasive bladder cancer expresses high level of GM3 ganglioside, whereas invasive tumors have low levels. Since glycosphingolipid synthesis in Golgi is modified greatly by a macrocyclic lactone isolated from fungi, brefeldin A (BFA), we studied effects of BFA on expression of glycosphingolipids and on invasiveness of bladder cancer cell lines. Only GM3 synthesis in invasive tumors was greatly enhanced upon treatment with BFA; synthesis of other glycosphingolipids with lacto-series type 2 or globo-series structure in both invasive and non-invasive tumors was not changed. Invasiveness of bladder cancer cells was greatly decreased in association with the great increase of GM3 synthesis induced by BFA treatment. Level of sialyl-Lex expressed in invasive cell line YTS1, which provides the adhesive property of the cells to E-selectin, was unchanged upon BFA treatment. All the bladder cancer cell lines, regardless of invasiveness, highly express tetraspanin CD9. GM3 has been implicated as a co-factor of CD9 in control of tumor cell motility. Down-regulation of CD9 is associated with metastatic properties of tumor cells and survival of patients with colonic cancer. Therefore, enhanced synthesis of GM3 induced by BFA, causing decrease of invasiveness in bladder cancer, is ascribable to the capability of GM3 to interconnect integrin with CD9, in analogy to colonic cancer and perhaps many other types of cancer.