A Comparative Study of Patient-Derived Tumor Models of Pancreatic Ductal Adenocarcinoma Involving Orthotopic Implantation
A Comparative Study of Patient-Derived Tumor Models of Pancreatic Ductal Adenocarcinoma Involving Orthotopic Implantation
复制标题
涉及原位植入的胰腺导管腺癌患者源性肿瘤模型的比较研究
DOI：
10.1159/000521714
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发表时间：
2022
期刊：
影响因子：
5
通讯作者：
Ochiai Atsushi
中科院分区：
文献类型：
--
作者：
Yanagihara Kazuyoshi;Iino Yuki;Yokozaki Hiroshi;Kubo Takanori;Oda Tatsuya;Kubo Takashi;Komatsu Masayuki;Sasaki Hiroki;Ichikawa Hitoshi;Kuwata Takeshi;Seyama Toshio;Ochiai Atsushi
背景胰腺导管腺癌（PDA）的预后较差。因此，迫切需要新的治疗方法和临床前模型。在本研究中，我们试图开发更现实的实验模型，用于在PDA research.MethodsWe开发的患者来源的异种移植物（PDXs），建立PDX衍生的细胞系（PDCLs），并产生细胞系衍生的异种移植物（CDXs），我们集成创建13个匹配的“三重奏”-即，患者来源的肿瘤模型的PDA。然后，我们比较和对比这三个模型systems.ResultsOrthotopic植入（OI）的PDCLs导致肿瘤的发生和转移到肝脏和腹膜之间的组织学和分子变化。OI-CDX和OI-PDX与传代肿瘤的形态学比较显示，原始肿瘤的组织病理学特征在两种模型中均得以保持。PDX肿瘤中的分子改变（包括KRAS、TP 53、SMAD 4和CDKN 2A的分子改变）与相应PDCL和CDX肿瘤中的分子改变相似。当基因表达水平的PDCLs，异位肿瘤，OI肿瘤进行了比较，远处转移促进基因CXCR 4特异性上调OI肿瘤，其免疫组化资料表明上皮间质转化和腺鳞状trans-differentiation.ConclusionThese患者来源的肿瘤模型提供了有用的工具，用于监测反应的抗肿瘤药物和研究PDA生物学。
BackgroundPancreatic ductal adenocarcinoma (PDA) is associated with very poor prognoses. Therefore, new therapies and preclinical models are urgently needed. In the present study, we sought to develop more realistic experimental models for use in PDA research.MethodsWe developed patient-derived xenografts (PDXs), established PDX-derived cell lines (PDCLs), and generated cell line-derived xenografts (CDXs), which we integrated to create 13 matched “trios”–ie, patient-derived tumor models of PDA. We then compared and contrasted histological and molecular alterations between these three model systems.ResultsOrthotopic implantation (OI) of the PDCLs resulted in tumorigenesis and metastases to the liver and peritoneum. Morphological comparisons of OI-CDXs and OI-PDXs with passaged tumors revealed that the histopathological features of the original tumor were maintained in both models. Molecular alterations in PDX tumors (including those to KRAS, TP53, SMAD4, and CDKN2A) were similar to those in the respective PDCLs and CDX tumors. When gene expression levels in the PDCLs, ectopic tumors, and OI tumors were compared, the distant metastasis-promoting gene CXCR4 was specifically upregulated in OI tumors, whose immunohistochemical profiles suggested epithelial-mesenchymal transition and adeno-squamous trans-differentiation.ConclusionThese patient-derived tumor models provide useful tools for monitoring responses to antineoplastic agents and for studying PDA biology.
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影响因子：
9.7
作者：
Li, Xuqi;Ma, Qingyong;Xu, Qinhong;Liu, Han;Lei, Jianjun;Duan, Wanxing;Bhat, Kruttika;Wang, Fengfei;Wu, Erxi;Wang, Zheng
通讯作者：
Wang, Zheng
DOI：
10.1073/pnas.89.12.5645
发表时间：
1992-06-15
影响因子：
11.1
作者：
FU, XY;GUADAGNI, F;HOFFMAN, RM
通讯作者：
HOFFMAN, RM
影响因子：
50.3
作者：
Andricovich J;Perkail S;Kai Y;Casasanta N;Peng W;Tzatsos A
通讯作者：
Tzatsos A
影响因子：
4.6
作者：
Katano I;Hanazawa A;Otsuka I;Yamaguchi T;Mochizuki M;Kawai K;Ito R;Goto M;Kagawa T;Takahashi T
通讯作者：
Takahashi T
影响因子：
28.2
作者：
Drapkin BJ;George J;Christensen CL;Mino-Kenudson M;Dries R;Sundaresan T;Phat S;Myers DT;Zhong J;Igo P;Hazar-Rethinam MH;Licausi JA;Gomez-Caraballo M;Kem M;Jani KN;Azimi R;Abedpour N;Menon R;Lakis S;Heist RS;Büttner R;Haas S;Sequist LV;Shaw AT;Wong KK;Hata AN;Toner M;Maheswaran S;Haber DA;Peifer M;Dyson N;Thomas RK;Farago AF
通讯作者：
Farago AF