期刊
NATURE MEDICINE
卷 23, 期 7, 页码 890-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4352
关键词
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资金
- Danish Cancer Society [R56-A3342, R124-A7862]
- Novo Nordisk Foundation (Hallas Moller Stipend)
- European Research Council [ERC-2015-CoG-682881-MATRICAN]
- Ragnar Soderberg Foundation Sweden [N19/15]
- Cancerfonden Sweden [CAN 2016/283]
- Innovation Foundation Denmark [1311-00010B]
- National Health and Medical Research Council (NHMRC) Australia [APP1129766]
- Danish Council for Independent Research YDUN grant [1084181001]
- Novo Nordisk Fonden [NNF12OC1015992] Funding Source: researchfish
- The Danish Cancer Society [R124-A7862] Funding Source: researchfish
The extracellular matrix (ECM) is a master regulator of cellular phenotype and behavior. It has a crucial role in both normal tissue homeostasis and disease pathology. Here we present a fast and efficient approach to enhance the study of ECM composition and structure. Termed in situ decellularization of tissues (ISDoT), it allows whole organs to be decellularized, leaving native ECM architecture intact. These three-dimensional decellularized tissues can be studied using high-resolution fluorescence and second harmonic imaging, and can be used for quantitative proteomic interrogation of the ECM. Our method is superior to other methods tested in its ability to preserve the structural integrity of the ECM, facilitate high-resolution imaging and quantitatively detect ECM proteins. In particular, we performed high-resolution sub-micron imaging of matrix topography in normal tissue and over the course of primary tumor development and progression to metastasis in mice, providing the first detailed imaging of the metastatic niche. These data show that cancer-driven ECM remodeling is organ specific, and that it is accompanied by comprehensive changes in ECM composition and topological structure. We also describe differing patterns of basement-membrane organization surrounding different types of blood vessels in healthy and diseased tissues. The ISDoT procedure allows for the study of native ECM structure under normal and pathological conditions in unprecedented detail.
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