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Directional cell movement through tissues is controlled by exosome secretion

Directional cell movement through tissues is critical for multiple biological processes and requires maintenance of polarity in the face of complex environmental cues. Here we use intravital imaging to demonstrate that secretion of exosomes from late endosomes is required for directionally persisten...

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Published in:Nature communications 2015-05, Vol.6 (1), p.7164-7164, Article 7164
Main Authors: Sung, Bong Hwan, Ketova, Tatiana, Hoshino, Daisuke, Zijlstra, Andries, Weaver, Alissa M.
Format: Article
Language:English
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Summary:Directional cell movement through tissues is critical for multiple biological processes and requires maintenance of polarity in the face of complex environmental cues. Here we use intravital imaging to demonstrate that secretion of exosomes from late endosomes is required for directionally persistent and efficient in vivo movement of cancer cells. Inhibiting exosome secretion or biogenesis leads to defective tumour cell migration associated with increased formation of unstable protrusions and excessive directional switching. In vitro r escue experiments with purified exosomes and matrix coating identify adhesion assembly as a critical exosome function that promotes efficient cell motility. Live-cell imaging reveals that exosome secretion directly precedes and promotes adhesion assembly. Fibronectin is found to be a critical motility-promoting cargo whose sorting into exosomes depends on binding to integrins. We propose that autocrine secretion of exosomes powerfully promotes directionally persistent and effective cell motility by reinforcing otherwise transient polarization states and promoting adhesion assembly. How cells maintain directional polarity when migrating through a complex environment is not well understood. Here Sung et al. show that autocrine exosome secretion is required for persistent and efficient in vivo cancer cell motility and promotes assembly of adhesion complexes by delivering fibronectin-bound exosomes.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms8164