Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma.
Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma.
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DOI：
10.1186/s13045-016-0318-6
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发表时间：
2016-09-21
影响因子：
28.5
通讯作者：
Wei JJ
中科院分区：
文献类型：
--
作者：
Dong R;Qiang W;Guo H;Xu X;Kim JJ;Mazar A;Kong B;Wei JJ
通过将原始患者的肿瘤组织移植到免疫缺陷小鼠中来产生患者来源的异种移植物（PDX）。与来源于细胞系的异种移植模型不同，PDX模型可以更好地保留原始患者和分子途径的组织病理学。高级别浆液性癌（HGSC）是一种致命的卵巢/输卵管癌，其对目前化疗的反应因患者的差异而差异很大。因此，PDX模型可以为研究和测试每个患者的治疗方案提供有价值的工具。在这项研究中，分析了来自9个HGSC的200多个PDX肿瘤，以研究源自HGSC的PDX肿瘤的性质和行为。PDX肿瘤连续传代（从P0至P4），并将肿瘤原位移植到卵巢囊下或皮下。对200多只PDX荷瘤小鼠的肿瘤组织学和分子标志物进行比较分析，发现与原发性肿瘤相比，肿瘤保持了相似的组织学、干细胞群以及大多数测试的致癌标志物的表达。然而，还注意到PDX肿瘤中类固醇激素受体的显著损失和免疫应答基因的表达改变。 我们的研究结果提供了大量关于HGSC PDX肿瘤特征的新信息，这将对HGSC的个性化治疗和新药开发有价值。本文的在线版本（doi：10.1186/s13045-016-0318-6）包含补充材料，可供授权用户使用。
Patient derived xenografts (PDX) are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4) and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC. The online version of this article (doi:10.1186/s13045-016-0318-6) contains supplementary material, which is available to authorized users.
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作者：
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