Relationship Between Increased Fucosylation and Metastatic Potential in Colorectal Cancer (Retracted Article)
Relationship Between Increased Fucosylation and Metastatic Potential in Colorectal Cancer (Retracted Article)
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DOI：
10.1093/jnci/djw210
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发表时间：
2016-09-01
影响因子：
10.3
通讯作者：
Kato, Junji
中科院分区：
文献类型：
--
作者：
Osuga, Takahiro;Takimoto, Rishu;Kato, Junji
背景：岩藻糖被用于修饰不同的分子，参与血型测定、免疫反应和信号转导途径。我们最近报道，岩藻糖基转移酶3和/或6的活性增强促进了转化生长因子-β介导的上皮间充质转化，并与结直肠癌转移潜能的增加有关，这表明结直肠癌细胞需要岩藻糖。考虑到这一点，我们研究了大肠癌细胞对L岩藻糖的需求，并开发了岩藻糖结合纳米粒作为载体来输送针对大肠癌的抗癌药物。方法：本研究首先用生物素标记的褐藻凝集素免疫组织化学方法检测了50例大肠癌组织中岩藻糖化蛋白的表达。然后，我们用三个大肠癌细胞系进行了L岩藻糖摄取实验。最后，我们开发了岩藻糖结合的纳米颗粒作为抗癌药物SN38的载体，并在小鼠异种移植模型(每组6只小鼠)中检测了对肿瘤生长的抑制作用。结果：血管侵犯程度、临床分期和AAL染色强度评分之间存在显著的统计学关系(P
Background: Fucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-beta-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC.Methods: In this study, we first examined the expression of fucosylated proteins in 50cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided.Results: We found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P