High-grade serous ovarian cancer cell lines exhibit heterogeneous responses to growth factor stimulation.
High-grade serous ovarian cancer cell lines exhibit heterogeneous responses to growth factor stimulation.
复制标题
高级浆液卵巢癌细胞系对生长因子刺激表现出异质反应。
DOI：
10.1186/s12935-015-0263-4
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发表时间：
2015
影响因子：
5.8
通讯作者：
Kreeger PK
中科院分区：
文献类型：
--
作者：
Bourgeois DL;Kabarowski KA;Porubsky VL;Kreeger PK
驱动卵巢癌发生和发展的因素尚不清楚。最近的报道已经确定了代表高级别浆液性卵巢癌（HGSOC）基因组模式的细胞系，其中超过90%的肿瘤具有TP53突变。然而，许多具有代表性的细胞系尚未被广泛使用，因此尚不清楚这些细胞系是否捕获了作为该疾病特征的变异性。我们研究了6种tp53突变的HGSOC细胞系（Caov3、Caov4、OV90、OVCA432、OVCAR3和OVCAR4）的迁移、MMP2表达、增殖和VEGF分泌等在肿瘤进展中起关键作用的行为。除了比较细胞系之间的基线变化外，我们还确定了这些行为如何响应与卵巢癌进展相关的四种生长因子：HB-EGF、NRG1β、IGF1和HGF。每种行为的基线水平在不同的细胞系中有所不同，这种变化与肿瘤中的变化相当。所有四种生长因子都影响细胞增殖或VEGF分泌，HB-EGF、NRG1β和HGF影响至少两种细胞系的伤口闭合或MMP2表达。生长因子诱导的反应显示出实质性的异质性，细胞系对所有四种生长因子敏感，对生长因子的一个子集敏感，或对任何生长因子都不敏感，这取决于感兴趣的反应。主成分分析表明，数据聚集在一起是基于细胞系而不是生长因子的身份，这表明反应取决于肿瘤细胞的内在品质，而不是生长因子。不同细胞系间存在显著差异，与HGSOC的异质性一致。本文的在线版本（doi:10.1186/s12935-015- 0264 -4）包含补充材料，可供授权用户使用。
The factors driving the onset and progression of ovarian cancer are not well understood. Recent reports have identified cell lines that are representative of the genomic pattern of high-grade serous ovarian cancer (HGSOC), in which greater than 90 % of tumors have a mutation in TP53. However, many of these representative cell lines have not been widely used so it is unclear if these cell lines capture the variability that is characteristic of the disease. We investigated six TP53-mutant HGSOC cell lines (Caov3, Caov4, OV90, OVCA432, OVCAR3, and OVCAR4) for migration, MMP2 expression, proliferation, and VEGF secretion, behaviors that play critical roles in tumor progression. In addition to comparing baseline variation between the cell lines, we determined how these behaviors changed in response to four growth factors implicated in ovarian cancer progression: HB-EGF, NRG1β, IGF1, and HGF. Baseline levels of each behavior varied across the cell lines and this variation was comparable to that seen in tumors. All four growth factors impacted cell proliferation or VEGF secretion, and HB-EGF, NRG1β, and HGF impacted wound closure or MMP2 expression in at least two cell lines. Growth factor-induced responses demonstrated substantial heterogeneity, with cell lines sensitive to all four growth factors, a subset of the growth factors, or none of the growth factors, depending on the response of interest. Principal component analysis demonstrated that the data clustered together based on cell line rather than growth factor identity, suggesting that response is dependent on intrinsic qualities of the tumor cell rather than the growth factor. Significant variation was seen among the cell lines, consistent with the heterogeneity of HGSOC. The online version of this article (doi:10.1186/s12935-015-0263-4) contains supplementary material, which is available to authorized users.