Proteomic alterations of fibroblasts induced by ovarian cancer cells reveal potential cancer targets
Proteomic alterations of fibroblasts induced by ovarian cancer cells reveal potential cancer targets
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卵巢癌细胞诱导的成纤维细胞的蛋白质组改变揭示了潜在的癌症靶点
DOI：
10.4149/neo_2018_101
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发表时间：
2018-01-01
期刊：
影响因子：
3
通讯作者：
Xu, C. J.
中科院分区：
文献类型：
--
作者：
Zhang, X. Y.;Hong, S. S.;Xu, C. J.
卵巢癌常见的扩散方式是腹膜种植。脱落的卵巢癌细胞在腹腔内的生长与肿瘤微环境密切相关。癌症相关成纤维细胞在肿瘤微环境中至关重要。成纤维细胞活化过程中蛋白质表达的变化尚不明确。本研究检测了卵巢癌细胞诱导的成纤维细胞中的蛋白质变化，并通过二维凝胶电泳和质谱探讨了潜在的生物学相关性。我们的数据显示，与卵巢癌细胞共培养的成纤维细胞中，CENPE、BAG2、SOD2、GDI2、CORO1C、CFL1、DSTN、CALD1、PHGDH、PDHA1、AKR1B1、TST和TBCA蛋白水平显着上调，而HSPB1、P4HB和VIM显着下调。然而，通过蛋白质印迹分析证实只有BAG2、SOD2和CORO1C蛋白显着增加。差异表达的蛋白质主要涉及代谢过程、细胞成分组织、刺激反应、多细胞生物过程、定位、蛋白质解聚、细胞衰老和有丝分裂途径。这些数据表明，成纤维细胞在被卵巢癌细胞诱导后，蛋白质表达模式发生改变，并参与导致肿瘤进展的多个细胞过程。差异表达的蛋白质应被视为癌症治疗的靶点。
The common spread pattern of ovarian cancer is peritoneal implantation. The growth of the shed ovarian cancer cells in the peritoneal cavity is closely related to the tumor microenvironment. Cancer-associated fibroblasts are vital in the tumor microenvironment. It is not clearly defined that the protein expression alters during the activating process of fibroblasts. This study detected the protein alterations in fibroblasts induced by ovarian cancer cells and explored the potential biological relevance through two-dimensional gel electrophoresis and mass spectrometry. Our data showed that the level of CENPE, BAG2, SOD2, GDI2, CORO1C, CFL1, DSTN, CALD1, PHGDH, PDHA1, AKR1B1, TST and TBCA proteins were significantly up-regulated in the fibroblasts co-cultured with ovarian cancer cells, whereas HSPB1, P4HB and VIM were significantly down-regulated. However, only BAG2, SOD2 and CORO1C proteins were confirmed to be significantly increased by western blot analysis. The differentially expressed proteins were mainly involved in metabolic processes, cellular component organization, responses to stimulus, multicellular organismal processes, localization, protein depolymerization, cellular senescence and the mitotic pathway. These data demonstrated that fibroblasts had an altered protein expression pattern after being induced by ovarian cancer cells, and participated in multiple cell processes resulting in tumor progression. The differentially expressed proteins should be considered as targets for cancer treatment.