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Effect of ovarian cancer ascites on SKOV-3 cells proteome: new proteins associated with aggressive phenotype in epithelial ovarian cancer.
Proteome Science ( IF 2 ) Pub Date : 2018-02-13 , DOI: 10.1186/s12953-018-0133-9
Alfredo Toledo-Leyva 1, 2 , Julio César Villegas-Pineda 1, 2 , Sergio Encarnación-Guevara 3 , Dolores Gallardo-Rincón 4 , Patricia Talamás-Rohana 1
Affiliation  

BACKGROUND Epithelial ovarian cancer is the second most lethal gynecological cancer worldwide. Ascites can be found in all clinical stages, however in advanced disease stages IIIC and IV it is more frequent and could be massive, associated with worse prognosis. Due to the above, it was our interest to understanding how the ascites of ovarian cancer patients induces the mechanisms by which the cells present in it acquire a more aggressive phenotype and to know new proteins associated to this process. METHODS A proteomic analysis of SKOV-3 cells treated with five different EOC ascites was performed by two-dimensional electrophoresis coupled to MALDI-TOF. The level of expression of the proteins of interest was validated by RT-PCR because several of these proteins have only been reported at the messenger level. RESULTS Among the proteins identified that increased their expression in ascites-treated SKOV-3 cells, were Ran GTPase, ZNF268, and Synaptotagmin like-3. On the other hand, proteins that were negatively regulated by ascites were HLA-I, HSPB1, ARF1, Synaptotagmin 1, and hnRNPH1, among others. Furthermore, an interactome for every one of these proteins was done in order to identify biological processes, molecular actions, and cellular components in which they may participate. CONCLUSIONS Identified proteins participate in cellular processes highly relevant to the aggressive phenotype such as nuclear transport, regulation of gene expression, vesicular trafficking, evasion of the immune response, invasion, metastasis, and in resistance to chemotherapy. These proteins may represent a source of information which has the potential to be evaluated for the design of therapies directed against these malignant cells that reside on ovarian cancer ascites.

中文翻译:

卵巢癌腹水对 SKOV-3 细胞蛋白质组的影响:与上皮性卵巢癌侵袭性表型相关的新蛋白质。

背景上皮性卵巢癌是全球第二大致命的妇科癌症。腹水可见于所有临床阶段,但在晚期疾病 IIIC 和 IV 期中,腹水更为常见,并且可能大量出现,与较差的预后相关。由于上述原因,我们有兴趣了解卵巢癌患者的腹水如何诱导其中存在的细胞获得更具攻击性的表型的机制,并了解与该过程相关的新蛋白质。方法 通过与 MALDI-TOF 偶联的二维电泳对用五种不同 EOC 腹水处理的 SKOV-3 细胞进行蛋白质组学分析。感兴趣的蛋白质的表达水平通过 RT-PCR 进行了验证,因为这些蛋白质中的一些仅在信使水平上被报道过。结果 在经腹水处理的 SKOV-3 细胞中确定的增加其表达的蛋白质中,有 Ran GTPase、ZNF268 和 Synaptotagmin like-3。另一方面,受腹水负调控的蛋白质有 HLA-I、HSPB1、ARF1、Synaptotagmin 1 和 hnRNPH1 等。此外,对这些蛋白质中的每一种都进行了相互作用组,以识别它们可能参与的生物过程、分子作用和细胞成分。结论 鉴定的蛋白质参与与侵袭性表型高度相关的细胞过程,例如核转运、基因表达的调节、囊泡运输、免疫反应的逃避、侵袭、转移和对化疗的抵抗。
更新日期:2019-11-01
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