期刊
MOLECULAR ONCOLOGY
卷 17, 期 9, 页码 1699-1725出版社
WILEY
DOI: 10.1002/1878-0261.13369
关键词
3D models; collective migration; directional migration; heterogeneity; imaging; protrusions
类别
Cancer cells can migrate collectively and form heteroclonal cell clusters through subcellular actin-rich protrusions. Disruption of cytoskeletal dynamics impairs collective migration, while myosin II activation is necessary for multicellular movements. The attraction of cell clusters may be mediated by secreted soluble factors, as evidenced by inhibition experiments and the chemoattracting activity of conditioned culture media.
Metastasisation occurs through the acquisition of invasive and survival capabilities that allow tumour cells to colonise distant sites. While the role of multicellular aggregates in cancer dissemination is acknowledged, the mechanisms that drive the formation of multiclonal cell aggregates are not fully elucidated. Here, we show that cancer cells of different tissue of origins can perform collective directional migration and can actively form heteroclonal aggregates in 3D, through a proliferation-independent mechanism. Coalescence of distant cell clusters is mediated by subcellular actin-rich protrusions and multicellular outgrowths that extend towards neighbouring aggregates. Coherently, perturbation of cytoskeletal dynamics impairs collective migration while myosin II activation is necessary for multicellular movements. We put forward the hypothesis that cluster attraction is mediated by secreted soluble factors. Such a hypothesis is consistent with the abrogation of aggregation by inhibition of PI3K/AKT/mTOR and MEK/ERK, the chemoattracting activity of conditioned culture media and with a wide screening of secreted proteins. Our results present a novel collective migration model and shed light on the mechanisms of formation of heteroclonal aggregates in cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据