Aubert M, Panicot-Dubois L, Crotte C, Sbarra V, Lombardo D, Sadoulet M O, Mas E
Inserm Unité 260. Unité de Recherche de Physiopathologie des Régulations Hormono-Nutritionnelles, Marseille, France.
Int J Cancer. 2000 Nov 15;88(4):558-65. doi: 10.1002/1097-0215(20001115)88:4<558::aid-ijc7>3.0.co;2-b.
Several alpha(1,3/1,4) fucosyltransferases expressed in human pancreatic cancer cells can participate in the biosynthesis of cell surface sialyl-Lewis a and sialyl-Lewis x antigens that contribute to hematogenous metastatis. Previously, we observed a significant increase of the alpha(1,4) fucosyltransferase activity in tumoral pancreatic cell lines, suggesting that FUT3 could be involved in the sialyl-Lewis antigen expression. Therefore, we invalidated the expression of FUT3 by expressing FUT3 antisense sequence in the human pancreatic tumor BxPC-3 cell line, which expresses the alpha(1,4) fucosyltransferase activity and harbors the cell surface sialyl-Lewis antigens. The decrease of FUT3 transcript after transfection of antisense cDNA of FUT3 in these cells results in a substantial reduction of sialyl-Lewis antigen expression on cell surface. This decreased antigen expression was associated with an inhibition of adhesive properties to E-selectin and a decrease of metastatic power of FUT3 antisense-transfected BxPC-3 cells as tested in nude mice. Our study provides evidence that the expression level of FUT3 may regulate the expression of sialyl-Lewis a and sialyl-Lewis x surface antigens and consequently could play an important role in metastatic properties of human pancreatic cancer cells.
几种在人胰腺癌细胞中表达的α(1,3/1,4)岩藻糖基转移酶可参与细胞表面唾液酸化路易斯a和唾液酸化路易斯x抗原的生物合成，这些抗原有助于血行转移。此前，我们观察到肿瘤性胰腺细胞系中α(1,4)岩藻糖基转移酶活性显著增加，提示FUT3可能参与唾液酸化路易斯抗原的表达。因此，我们通过在人胰腺肿瘤BxPC-3细胞系中表达FUT3反义序列，使FUT3的表达无效，该细胞系表达α(1,4)岩藻糖基转移酶活性并含有细胞表面唾液酸化路易斯抗原。在这些细胞中转染FUT3反义cDNA后，FUT3转录本减少，导致细胞表面唾液酸化路易斯抗原表达大幅降低。这种抗原表达的降低与对E-选择素的黏附特性抑制以及在裸鼠中测试的FUT3反义转染的BxPC-3细胞转移能力的降低相关。我们的研究提供了证据，表明FUT3的表达水平可能调节唾液酸化路易斯a和唾液酸化路易斯x表面抗原的表达，因此可能在人胰腺癌细胞的转移特性中发挥重要作用。
