Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma.
Cancer-associated fibroblasts mediate cancer progression and remodel the tumouroid stroma.
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癌症相关成纤维细胞介导癌症进展并重塑肿瘤样间质。
DOI：
10.1038/s41416-020-0973-9
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发表时间：
2020-09
影响因子：
8.8
通讯作者：
Cheema U
中科院分区：
文献类型：
--
作者：
Pape J;Magdeldin T;Stamati K;Nyga A;Loizidou M;Emberton M;Cheema U
癌症相关成纤维细胞（CAF）是高度分化的异质性癌症基质细胞，可促进肿瘤生长、血管生成和基质重塑。我们利用了先前开发的结直肠癌3D体外模型的改编版本，该模型由癌块和周围的间质隔室组成。我们比较了无细胞间质周围、“健康”或正常细胞间质和癌性间质的癌症侵袭。对于癌性间质，我们纳入了六个患者来源的CAF样本，以研究它们对癌症生长、血管网络形成和重塑的不同影响。CAF增强了浸润性癌块的距离和表面积，同时抑制了血管样网络的形成。这些过程与肝细胞生长因子（HGF）、金属肽酶抑制剂1（TIMP 1）和纤蛋白-5（FBLN 5）的上调相关。先前形成的内皮结构的血管重塑通过复杂网络的破坏发生，并且与血管内皮生长因子（VEGFA）的上调和血管内皮钙粘蛋白（VE-钙粘蛋白）的下调相关。这些结果支持在仿生3D体外框架内CAFs在促进癌症侵袭中的直接作用，以及它们在驱动血管发生和血管生成中的关键功能。
Cancer-associated fibroblasts (CAFs) are highly differentiated and heterogeneous cancer-stromal cells that promote tumour growth, angiogenesis and matrix remodelling. We utilised an adapted version of a previously developed 3D in vitro model of colorectal cancer, composed of a cancer mass and the surrounding stromal compartment. We compared cancer invasion with an acellular stromal surround, a “healthy” or normal cellular stroma and a cancerous stroma. For the cancerous stroma, we incorporated six patient-derived CAF samples to study their differential effects on cancer growth, vascular network formation and remodelling. CAFs enhanced the distance and surface area of the invasive cancer mass whilst inhibiting vascular-like network formation. These processes correlated with the upregulation of hepatocyte growth factor (HGF), metallopeptidase inhibitor 1 (TIMP1) and fibulin-5 (FBLN5). Vascular remodelling of previously formed endothelial structures occurred through the disruption of complex networks, and was associated with the upregulation of vascular endothelial growth factor (VEGFA) and downregulation in vascular endothelial cadherin (VE-Cadherin). These results support, within a biomimetic 3D, in vitro framework, the direct role of CAFs in promoting cancer invasion, and their key function in driving vasculogenesis and angiogenesis.
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DOI：
10.2147/ccid.s50046
发表时间：
2014
期刊：
Clinical, cosmetic and investigational dermatology
影响因子：
--
作者：
Darby IA;Laverdet B;Bonté F;Desmoulière A
通讯作者：
Desmoulière A
影响因子：
7.7
作者：
Madsen CD;Pedersen JT;Venning FA;Singh LB;Moeendarbary E;Charras G;Cox TR;Sahai E;Erler JT
通讯作者：
Erler JT
影响因子：
--
作者：
Li WW;Wang HY;Nie X;Liu YB;Han M;Li BH
通讯作者：
Li BH
影响因子：
4.5
作者：
Choi SY;Sung R;Lee SJ;Lee TG;Kim N;Yoon SM;Lee EJ;Chae HB;Youn SJ;Park SM
通讯作者：
Park SM
影响因子：
8
作者：
Jeanes, A.;Gottardi, C. J.;Yap, A. S.
通讯作者：
Yap, A. S.