Institut Curie, PSL Research University, CNRS, UMR 144 - Cell Biology and Cancer, 75005 Paris, France
University Paris Descartes, 12 rue de l'Ecole de Médecine, 75006 Paris, France.
J Cell Sci. 2019 Mar 15;132(6):jcs220277. doi: 10.1242/jcs.220277.
In the early stages of metastasis, cancer cells exit the primary tumor and enter the vasculature. Although most studies have focused on the tumor invasive front, cancer cells from the tumor core can also potentially metastasize. To address cell motility in the tumor core, we imaged tumor explants from spontaneously forming tumors in mice in real time using long-term two-photon microscopy. Cancer cells in the tumor core are remarkably dynamic and exhibit correlated migration patterns, giving rise to local 'currents' and large-scale tissue dynamics. Although cells exhibit stop-and-start migration with intermittent pauses, pausing does not appear to be required during division. Use of pharmacological inhibitors indicates that migration patterns in tumors are actively driven by the actin cytoskeleton. Under these conditions, we also observed a relationship between migration speed and correlation length, suggesting that cells in tumors are near a jamming transition. Our study provides new insight into the dynamics of cancer cells in the tumor core, opening new avenues of research in understanding the migratory properties of cancer cells and later metastasis.This article has an associated First Person interview with the first author of the paper.
在转移的早期阶段，癌细胞从原发性肿瘤中逸出并进入脉管系统。尽管大多数研究都集中在肿瘤侵袭前沿，但肿瘤核心的癌细胞也有可能转移。为了解决肿瘤核心中的细胞迁移问题，我们使用长期双光子显微镜实时成像来自自发形成的小鼠肿瘤的肿瘤外植体。肿瘤核心中的癌细胞非常活跃，表现出相关的迁移模式，产生局部“电流”和大规模的组织动力学。尽管细胞表现出带有间歇性停顿的停止-启动迁移，但在分裂过程中似乎不需要停顿。药理学抑制剂的使用表明，肿瘤中的迁移模式是由肌动蛋白细胞骨架主动驱动的。在这些条件下，我们还观察到迁移速度和相关长度之间的关系，表明肿瘤中的细胞接近阻塞转变。我们的研究为肿瘤核心中癌细胞的动力学提供了新的见解，为理解癌细胞的迁移特性和随后的转移开辟了新的研究途径。本文附有该论文第一作者的第一人称采访。
