The coordinated movement of cell collectives is essential for normal epithelial tissue development, maintenance, and cancer progression. Here, we report on a minimal 3D extracellular matrix (ECM) system wherein both invasive collective migration (ICM) and rotational collective migration (RCM) arise spontaneously from individually seeded epithelial cells of mammary and hepatic origin, regardless of whether they express adherens junctions, and lead to ductal-like and acinar-like structures, respectively. Quantitative microscopy and cellular Potts modeling reveal that initial differences in cell protrusion dynamics and matrix-remodeling localization generate RCM and ICM behavior in confining 3D ECM. Matrix-remodeling activity by matrix metalloproteinases (MMPs) is localized to the base of protrusions in cells that initiate ICM, whereas RCM does not require MMPs and is associated with ITGβ1-mediated remodeling localized globally around the cell body. Further analysis in vitro and in vivo supports the concept that distinct matrix-remodeling strategies encode collective migration behaviors and tissue structure.

中文翻译：

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整体与局部基质重塑驱动上皮细胞的旋转与侵袭集体迁移


细胞集合的协调运动对于正常的上皮组织发育、维持和癌症进展至关重要。在这里，我们报告了一个最小的 3D 细胞外基质 （ECM） 系统，其中侵袭性集体迁移 （ICM） 和旋转集体迁移 （RCM） 都自发地产生自发地来自单独接种的乳腺和肝脏来源的上皮细胞，无论它们是否表达粘附连接，并导致导管样和腺泡样结构，分别。定量显微镜和细胞 Potts 建模显示，细胞突起动力学和基质重塑定位的初始差异在限制 3D ECM 中产生 RCM 和 ICM 行为。基质金属蛋白酶 （MMP） 的基质重塑活性定位于启动 ICM 的细胞中的突起底部，而 RCM 不需要 MMP，并且与位于细胞体周围全球的 ITGβ1 介导的重塑有关。体外和 体内的进一步分析 支持不同的基质重塑策略编码集体迁移行为和组织结构的概念。