Organotypic platform for studying cancer cell metastasis.
Organotypic platform for studying cancer cell metastasis.
复制标题
研究癌细胞转移的器官型平台。
DOI：
10.1016/j.yexcr.2021.112527
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发表时间：
2021-04-15
影响因子：
3.7
通讯作者：
Yin H
中科院分区：
文献类型：
--
作者：
Spennati G;Horowitz LF;McGarry DJ;Rudzka DA;Armstrong G;Olson MF;Folch A;Yin H
转移是癌症患者死亡率的主要原因。要迁移到遥远的部位，癌细胞需要适应其行为，以应对不同的组织环境。因此，在可以密切复制肿瘤微环境的模型中研究此过程至关重要。在这里，我们评估了器官肝脏和脑切片的使用来研究癌症转移。每天在培养物中每天监测切片的形态和生存能力参数，以评估其作为体外转移测定的现实3D组织平台的稳定性。使用这些切片，我们评估了MDA-MB-231乳腺癌细胞的侵袭以及被选择以增加运动性的亚群。我们表明，所选细胞的更具侵略性的侵袭不仅可能是由于其较低的刚度而导致的，而且可能是由于其较低的粘附力对周围组织而言。对于两个亚群，都观察到大脑和肝切片中不同的浸润模式。与肝切片相比（它们以间充质或集体迁移样模式迁移），细胞在脑切片中迁移得更快（具有变形虫模式）。 RAS/MAPK/ERK途径的抑制增加了细胞刚度和粘附力，从而降低了侵袭性。这些结果说明了与大多数体外模型相比，在癌细胞转移期间，器官型组织切片在癌细胞转移过程中更紧密地模仿体内条件。
Metastasis is the leading cause of mortality in cancer patients. To migrate to distant sites, cancer cells would need to adapt their behaviour in response to different tissue environments. Thus, it is essential to study this process in models that can closely replicate the tumour microenvironment. Here, we evaluate the use of organotypic liver and brain slices to study cancer metastasis. Morphological and viability parameters of the slices were monitored daily over 3 days in culture to assess their stability as a realistic 3D tissue platform for in vitro metastatic assays. Using these slices, we evaluated the invasion of MDA-MB-231 breast cancer cells and of a subpopulation that was selected for increased motility. We show that the more aggressive invasion of the selected cells likely resulted not only from their lower stiffness, but also from their lower adhesion to the surrounding tissue. Different invasion patterns in the brain and liver slices were observed for both subpopulations. Cells migrated faster in the brain slices (with an amoeboid-like mode) compared to in the liver slices (where they migrated with mesenchymal or collective migration-like modes). Inhibition of the Ras/MAPK/ERK pathway increased cell stiffness and adhesion forces, which resulted in reduced invasiveness. These results illustrate the potential for organotypic tissue slices to more closely mimic in vivo conditions during cancer cell metastasis than most in vitro models.
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影响因子：
3.5
作者：
Cross, Sarah E.;Jin, Yu-Sheng;Gimzewski, James K.
通讯作者：
Gimzewski, James K.
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
3.2
作者：
Granitzny, Anne;Knebel, Jan;Hansen, Tanja
通讯作者：
Hansen, Tanja
影响因子：
7.5
作者：
Laemmermann, Tim;Sixt, Michael
通讯作者：
Sixt, Michael
影响因子：
3.9
作者：
Erdogan B;Webb DJ
通讯作者：
Webb DJ