Ranamukhaarachchi Sural K, Walker Alyssa, Tang Man-Ho, Leineweber William D, Lam Sophia, Rappel Wouter-Jan, Fraley Stephanie I
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Physics, University of California, San Diego, La Jolla, CA 92093, USA.
Dev Cell. 2025 Mar 24;60(6):871-884.e8. doi: 10.1016/j.devcel.2024.11.021. Epub 2024 Dec 19.
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.
细胞集体的协调运动对于正常上皮组织的发育、维持和癌症进展至关重要。在此，我们报告了一种最小的三维细胞外基质（ECM）系统，在该系统中，侵袭性集体迁移（ICM）和旋转集体迁移（RCM）分别自发地从乳腺和肝脏来源的单个接种上皮细胞中产生，无论它们是否表达黏附连接，并分别导致导管样和腺泡样结构。定量显微镜和细胞Potts模型显示，细胞突起动力学和基质重塑定位的初始差异在受限的三维ECM中产生RCM和ICM行为。基质金属蛋白酶（MMPs）的基质重塑活性定位于启动ICM的细胞突起基部，而RCM不需要MMPs，并且与整合素β1（ITGβ1）介导的围绕细胞体全局定位的重塑相关。体外和体内的进一步分析支持了不同的基质重塑策略编码集体迁移行为和组织结构这一概念。
