Organoid models of human and mouse ductal pancreatic cancer.
Organoid models of human and mouse ductal pancreatic cancer.
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DOI：
10.1016/j.cell.2014.12.021
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发表时间：
2015-01-15
期刊：
影响因子：
64.5
通讯作者：
Tuveson DA
中科院分区：
文献类型：
--
作者：
Boj SF;Hwang CI;Baker LA;Chio II;Engle DD;Corbo V;Jager M;Ponz-Sarvise M;Tiriac H;Spector MS;Gracanin A;Oni T;Yu KH;van Boxtel R;Huch M;Rivera KD;Wilson JP;Feigin ME;Öhlund D;Handly-Santana A;Ardito-Abraham CM;Ludwig M;Elyada E;Alagesan B;Biffi G;Yordanov GN;Delcuze B;Creighton B;Wright K;Park Y;Morsink FH;Molenaar IQ;Borel Rinkes IH;Cuppen E;Hao Y;Jin Y;Nijman IJ;Iacobuzio-Donahue C;Leach SD;Pappin DJ;Hammell M;Klimstra DS;Basturk O;Hruban RH;Offerhaus GJ;Vries RG;Clevers H;Tuveson DA
胰腺癌由于其诊断晚、治疗效果差，是最致命的恶性肿瘤之一。目前迫切需要易于处理的方法来识别和询问参与胰腺肿瘤发生的途径。我们从正常和肿瘤小鼠和人胰腺组织建立了类器官模型。胰腺类器官可以从切除的肿瘤和活检组织中快速生成，在冷冻保存后存活，并表现出导管和疾病阶段特异性特征。原位移植的肿瘤性类器官通过形成进展为局部浸润性和转移性癌的早期肿瘤来概括肿瘤发展的全谱。由于它们能够被遗传操纵，类器官是探索遗传合作的平台。对小鼠胰腺类器官的全面转录和蛋白质组学分析揭示了疾病进展过程中改变的基因和途径。人体组织中许多这些蛋白质变化的证实表明，类器官是发现这种致命恶性肿瘤特征的简单模型系统。
Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Karthaus WR;Iaquinta PJ;Drost J;Gracanin A;van Boxtel R;Wongvipat J;Dowling CM;Gao D;Begthel H;Sachs N;Vries RGJ;Cuppen E;Chen Y;Sawyers CL;Clevers HC
通讯作者：
Clevers HC
影响因子：
64.5
作者：
Gao D;Vela I;Sboner A;Iaquinta PJ;Karthaus WR;Gopalan A;Dowling C;Wanjala JN;Undvall EA;Arora VK;Wongvipat J;Kossai M;Ramazanoglu S;Barboza LP;Di W;Cao Z;Zhang QF;Sirota I;Ran L;MacDonald TY;Beltran H;Mosquera JM;Touijer KA;Scardino PT;Laudone VP;Curtis KR;Rathkopf DE;Morris MJ;Danila DC;Slovin SF;Solomon SB;Eastham JA;Chi P;Carver B;Rubin MA;Scher HI;Clevers H;Sawyers CL;Chen Y
通讯作者：
Chen Y
影响因子：
7.3
作者：
Cleveland, Megan H.;Sawyer, Jacob M.;Afelik, Solomon;Jensen, Jan;Leach, Steven D.
通讯作者：
Leach, Steven D.
DOI：
10.1073/pnas.0810111105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Jean-Paul, De La O.;Emerson, Lyska L.;Murtaugh, L. Charles
通讯作者：
Murtaugh, L. Charles