Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems.
Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems.
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DOI：
10.1371/journal.pone.0013002
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发表时间：
2010-09-27
期刊：
影响因子：
3.7
通讯作者：
Haab BB
中科院分区：
文献类型：
--
作者：
Maupin KA;Sinha A;Eugster E;Miller J;Ross J;Paulino V;Keshamouni VG;Tran N;Berens M;Webb C;Haab BB
选择性检测和靶向经历上皮-间质转化（EMT）的癌细胞的能力可能会改善治疗胰腺癌等癌症的方法。细胞糖基化的重塑先前与细胞分化有关，可能代表了EMT的一个有价值的分子靶点。作为研究EMT中糖基化改变本质的第一步，我们在三个体外模型系统中表征了糖基化相关基因的表达，每个模型系统都代表了胰腺癌EMT的一个互补方面。这些模型包括：1)tgf β诱导的EMT，它提供了状态之间的主动转换；2) 22个胰腺癌细胞系，代表上皮样或间充质样的最终分化状态；3)主动迁移细胞和静止细胞，这为迁移机制提供了一个视角。我们分析了涉及糖基化（生物合成、糖转运、聚糖结合等）或EMT的587个基因的表达数据。在前两种模型中，糖基因改变的发生率高于其他所有基因（p分别<0.05和<0.005），而在迁移模型中则没有。诱导emt模型和细胞系面板之间的几个功能主题是相同的，包括基质成分和蛋白聚糖的改变，糖胺聚糖的磺化；甘露糖受体家族成员；o -糖基化起始；以及某些形式的唾液酰化。Western blot检测甘露糖受体MRC2和o -糖基化酶GALNT3蛋白水平变化，Alcian Blue染色检测细胞表面硫酸化变化。糖基因的改变是癌症EMT的主要组成部分，其特征是基质成分、gag的硫酸化、甘露糖受体、o糖基化和特异性唾液化结构的改变。这些结果为靶向侵袭性和耐药形式的胰腺癌细胞提供了线索。
The ability to selectively detect and target cancer cells that have undergone an epithelial-mesenchymal transition (EMT) may lead to improved methods to treat cancers such as pancreatic cancer. The remodeling of cellular glycosylation previously has been associated with cell differentiation and may represent a valuable class of molecular targets for EMT. As a first step toward investigating the nature of glycosylation alterations in EMT, we characterized the expression of glycan-related genes in three in-vitro model systems that each represented a complementary aspect of pancreatic cancer EMT. These models included: 1) TGFβ-induced EMT, which provided a look at the active transition between states; 2) a panel of 22 pancreatic cancer cell lines, which represented terminal differentiation states of either epithelial-like or mesenchymal-like; and 3) actively-migrating and stationary cells, which provided a look at the mechanism of migration. We analyzed expression data from a list of 587 genes involved in glycosylation (biosynthesis, sugar transport, glycan-binding, etc.) or EMT. Glycogenes were altered at a higher prevalence than all other genes in the first two models (p<0.05 and <0.005, respectively) but not in the migration model. Several functional themes were shared between the induced-EMT model and the cell line panel, including alterations to matrix components and proteoglycans, the sulfation of glycosaminoglycans; mannose receptor family members; initiation of O-glycosylation; and certain forms of sialylation. Protein-level changes were confirmed by Western blot for the mannose receptor MRC2 and the O-glycosylation enzyme GALNT3, and cell-surface sulfation changes were confirmed using Alcian Blue staining. Alterations to glycogenes are a major component of cancer EMT and are characterized by changes to matrix components, the sulfation of GAGs, mannose receptors, O-glycosylation, and specific sialylated structures. These results provide leads for targeting aggressive and drug resistant forms of pancreatic cancer cells.
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影响因子：
11.5
作者：
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通讯作者：
Esko, JD
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82.9
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Karadimitris, Anastasios
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56.9
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