Capturing complex tumour biology in vitro: histological and molecular characterisation of precision cut slices

被引：94

作者：

Davies, Emma ^{[1
]}

Dong, Meng ^{[2
,3
]}

Gutekunst, Matthias ^{[2
,3
]}

Narhi, Katja ^{[4
]}

van Zoggel, Hanneke J. A. A. ^{[5
]}

Blom, Sami ^{[4
]}

Nagaraj, Ashwini ^{[4
]}

Metsalu, Tauno ^{[6
]}

Oswald, Eva ^{[7
]}

Erkens-Schulze, Sigrun ^{[5
]}

San Martin, Juan A. Delgado ^{[1
]}

Turkki, Riku ^{[4
]}

Wedge, Stephen R. ^{[1
]}

af Hallstrom, Taija M. ^{[4
]}

Schueler, Julia ^{[7
]}

van Weerden, Wytske M. ^{[5
]}

Verschuren, Emmy W. ^{[4
]}

Barry, Simon T. ^{[1
]}

van der Kuip, Heiko ^{[2
,3
]}

Hickman, John A. ^{[8
]}

机构：

[1] AstraZeneca, Biosci, Oncol iMed, Macclesfield SK10 4TG, Cheshire, England

[2] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany

[3] Univ Tubingen, D-70376 Stuttgart, Germany

[4] Univ Helsinki, FIMM, Helsinki, Finland

[5] Erasmus MC, Dept Urol, NL-3000 CA Rotterdam, Netherlands

[6] Univ Tartu, Inst Comp Sci, EE-50409 Tartu, Estonia

[7] Oncotest GmbH, D-79108 Freiburg, Germany

[8] Inst Rech Servier, F-75017 Paris, France

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

关键词：

ORGANOTYPIC CULTURE; CANCER; MODELS; HYPOXIA; EXPRESSION; TISSUES; MCF-7;

D O I：

10.1038/srep17187

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Precision-cut slices of in vivo tumours permit interrogation in vitro of heterogeneous cells from solid tumours together with their native microenvironment. They offer a low throughput but high content in vitro experimental platform. Using mouse models as surrogates for three common human solid tumours, we describe a standardised workflow for systematic comparison of tumour slice cultivation methods and a tissue microarray-based method to archive them. Cultivated slices were compared to their in vivo source tissue using immunohistochemical and transcriptional biomarkers, particularly of cellular stress. Mechanical slicing induced minimal stress. Cultivation of tumour slices required organotypic support materials and atmospheric oxygen for maintenance of integrity and was associated with significant temporal and loco-regional changes in protein expression, for example HIF-1 alpha. We recommend adherence to the robust workflow described, with recognition of temporal-spatial changes in protein expression before interrogation of tumour slices by pharmacological or other means.

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