Increase of rat colon carcinoma cells tumorigenicity by alpha(1-2) fucosyltransferase gene transfection
Increase of rat colon carcinoma cells tumorigenicity by alpha(1-2) fucosyltransferase gene transfection
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DOI：
10.1093/glycob/7.2.221
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发表时间：
1997-03-01
期刊：
影响因子：
4.3
通讯作者：
LePendu, J
中科院分区：
文献类型：
--
作者：
Goupille, C;Hallouin, F;LePendu, J
岩藻糖基化的组织血型抗原（例如 Lewis b、Lewis Y 和 H）在结肠癌中积累，并伴随着 α(1-2) 岩藻糖基转移酶活性的明显增加，α(1-2)岩藻糖基转移酶活性是这些抗原生物合成的关键酶。然而，α(1-2)岩藻糖基化结构的生物学意义尚不明确，我们用人H血型α(1-2)岩藻糖基转移酶cDNA转染了低致瘤性大鼠结肠癌细胞系，这导致细胞表面H抗原表达，同时唾液酸取代和游离β-半乳糖苷减少。免疫沉淀实验表明，H抗原基本上是由携带外显子v6编码的氨基酸序列的CD44变体携带的，转染的细胞在伤口愈合测定中显示出增加的运动性，而没有改变其增殖率，用空载体转染的亲本和对照细胞形成小肿瘤，当皮下注射到同系大鼠时，这些肿瘤总是在30天后消退。相比之下，α(1-2)岩藻糖基转移酶转染子仅能够形成进行性肿瘤，增加在裸鼠中也可见致瘤性。这些结果表明，α(1-2)岩藻糖基化抗原直接导致结肠癌细胞的侵袭性，这可以通过改变 CD44 变体的功能来实现。
Fucosylated histo-blood group antigens such as Lewis b, Lewis Y, and H accumulate in colon carcinoma and this is accompanied by a clear increase in alpha(1-2)fucosyltransferase activity, a key enzyme for the biosynthesis of these antigens. Yet the biological significance of alpha(1-2)fucosylated structures is not well defined, We have transfected a poorly tumorigenic rat colon carcinoma cell line with the human H blood group alpha(1-2)fucosyltransferase cDNA, This resulted in cell surface expression of H antigens with a concomitant decrease of sialic acid substituted and free beta-galactosides. Immunoprecipitation experiments showed that H antigens were essentially borne by variants of CD44 carrying amino acid sequences encoded by exon v6, The transfected cells showed increased motility in a wound healing assay, without changing their proliferation rates, Parental and control cells transfected with an empty vector formed small tumors that always regressed after 30 days when injected subcutaneously to syngeneic rats, In contrast, alpha(1-2)fucosyltransferase transfectants mere able to form progressive tumors, Increased tumorigenicity was also visible in nude mice, These results demonstrate that alpha(1-2)fucosylated antigens contribute directly to aggressiveness of colon carcinoma cells, This could occur by altering a function of CD44 variants.