Probing three-dimensional collective cancer invasion with DIGME.

Cancer convergence Pub Date : 2017-01-01 Epub Date: 2017-11-01 DOI:10.1186/s41236-017-0004-9
Amani A Alobaidi, Bo Sun
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Abstract

Background: Multicellular pattern formation plays an important role in developmental biology, cancer metastasis and wound healing. While many physical factors have been shown to regulate these multicellular processes, the role of ECM micro-to-meso scale geometry has been poorly understood in 3D collective cancer invasion.

Results: We have developed a mechanical-based strategy, Diskoid In Geometrically Micropatterned ECM (DIGME). DIGME allows easy engineering of the shape of 3D tissue organoid, the mesoscale ECM heterogeneity, and the fiber alignment of collagen-based ECM all at the same time. We have employed DIGME to study the 3D invasion of MDA-MB-231 diskoids in engineered collagen matrix. We find that the collective cancer invasion is closely regulated by the micro-to-meso scale geometry of the ECM.

Conclusions: We conclude that DIGME provides a simple yet powerful tool to probe 3D dynamics of tissue organoids in physically patterned microenvironments.

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利用 DIGME 探测三维集体癌症侵袭。
背景:多细胞模式的形成在发育生物学、癌症转移和伤口愈合中发挥着重要作用。虽然许多物理因素已被证明能调节这些多细胞过程,但人们对 ECM 微观到微观尺度几何在三维集体癌症侵袭中的作用还知之甚少:我们开发了一种基于机械的策略--Diskoid In Geometrically Micropatterned ECM (DIGME)。DIGME 可以轻松地同时设计三维组织器官的形状、中尺度 ECM 的异质性以及基于胶原蛋白的 ECM 的纤维排列。我们利用 DIGME 研究了 MDA-MB-231 盘状组织在工程胶原基质中的三维侵袭。我们发现,癌症的集体侵袭受到 ECM 微观到微观尺度几何形状的密切调控:我们得出的结论是:DIGME 提供了一种简单而强大的工具,可用于探测物理模式微环境中组织器官的三维动态。
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