Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines
Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines
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DOI：
10.1093/glycob/8.6.605
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发表时间：
1998-06-01
期刊：
影响因子：
4.3
通讯作者：
Sadoulet, MO
中科院分区：
文献类型：
--
作者：
Mas, E;Pasqualini, E;Sadoulet, MO
人类胰腺癌的特征是含有岩藻糖的表面血型抗原的改变，如H抗原、Lewis b、Lewis y和sialyl-Lewis。这些碳水化合物决定因素可以通过α(2，3)唾液酸基转移酶或α(1，2)岩藻糖基转移酶(Fuc-T)和α(1，3/1，4)岩藻糖基转移酶在(聚)N-乙酰乳糖胺链上的顺序作用来合成。因此，我们研究了7种岩藻糖基转移酶在正常胰腺组织、胰腺癌组织和4种胰腺癌细胞系中的表达和功能。RT-PCR检测癌细胞系、正常组织和肿瘤组织中FUT1、FUT2、FUT3、FUT4、FUT5和FUT7的转录水平。有趣的是，FUT6消息只在肿瘤组织中检测到。岩藻糖基转移酶的受体底物特异性分析表明，α(1，2)Fuc-T、α(1，3)Fuc-T和(1，4)Fuc-T在所有组织的微生物体中都有表达，苯基β-D-半乳糖苷、2‘-岩藻糖基乳糖、N-乙酰乳糖胺、3’-唾液酰基-N-乙酰乳糖胺和乳酸-N-二糖的岩藻糖掺入证明了这一点。然而，这些岩藻糖基转移酶的活性因组织而异。与正常组织相比，肿瘤组织和细胞系中的α(1，2)Fuc-T活性显著降低。相反，产生Lewis a和sialyl-Lewis a结构的α(1，4)Fuc-T和能够产生乳二岩藻四糖结构的α(1，3)Fuc-T的活性在SOJ-6和BxPC-3细胞中非常重要。这些增加与细胞表面Lewis a、sialyl-Lewis a和Lewis y的表达增强相关。与正常组织相比，参与sialyl-Lewis x结构合成的α(1，3)Fuc-T的活性在细胞系中没有明显的改变。但在SOJ-6和BxPC-3细胞株表面有sialyl-Lewis x抗原的优先表达，而在PANC-1和MiaPaca-2细胞上未检测到sialyl-Lewis x抗原的表达，提示几种α(1，3)Fuc-T可能参与了sialyl-Lewis x的合成。
Human pancreatic cancer is characterized by an alteration in fucose-containing surface blood group antigens such as H antigen, Lewis b, Lewis y, and sialyl-Lewis. These carbohydrate determinants can be synthesized by sequential action of alpha(2,3) sialyltransferases or alpha(1,2) fucosyltransferases (Fuc-T) and alpha(1,3/1,4) fucosyltransferases on (poly)N-acetyllactosamine chains. Therefore, the expression and the function of seven fucosyltransferases were investigated in normal and cancer pancreatic tissues and in four pancreatic carcinoma cell lines. Transcripts of FUT1, FUT2, FUT3, FUT4, FUT5, and FUT7 were detected by RT-PCR in carcinoma cell lines as well as in normal and tumoral tissues. Interestingly, the FUT6 message was only detected in tumoral tissues. Analysis of the acceptor substrate specificity for fucosyltransferases indicated that alpha(1,2) Fuc-T, alpha(1,3) Fuc-T, and (1,4) Fuc-T were expressed in microsome preparations of all tissues as demonstrated by fucose incorporation into phenyl beta-D-galactoside, 2'-fucosyllactose, N-acetyllactosamine, 3'-sialyl-N-acetyllactosamine, and lacto-N-biose. However, these fucosyltransferase activities varied between tissues. A substantial decrease of alpha(1,2) Fuc-T activity was observed in tumoral tissues and cell lines compared to normal tissues. Conversely, the activity of alpha(1,4) Fuc-T, which generates Lewis a and sialyl-Lewis a structures, and that of alpha(1,3) Fuc-T, able to generate a lactodifucotetraose structure, were very important in SOJ-6 and BxPC-3 cell lines. These increases correlated with an enhanced expression of Lewis a, sialyl-Lewis a, and Lewis y on the cell surface. The activity of alpha(1,3) Fuc-T, which participates in the synthesis of the sialyl-Lewis x structure, was not significantly modified in cell lines compared to normal tissues. However, the sialyl-Lewis x antigen was expressed preferentially on the surface of SOJ-6 and BxPC-3 cell lines but was not detected on Panc-1 and MiaPaca-2 cell lines suggesting that several alpha(1,3) Fuc-T might be involved in sialyl-Lewis x synthesis.