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Cell Rep. 2013 Dec 12;5(5):1159-68. doi: 10.1016/j.celrep.2013.10.050. Epub 2013 Nov 27.

Exosome secretion is enhanced by invadopodia and drives invasive behavior.

Author information

1
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
2
Department of Microbiology and Immunology, University of Miami Medical School, Miami, FL 33101, USA.
3
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
4
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: alissa.weaver@vanderbilt.edu.

Abstract

Unconventional secretion of exosome vesicles from multivesicular endosomes (MVEs) occurs across a broad set of systems and is reported to be upregulated in cancer, where it promotes aggressive behavior. However, regulatory control of exosome secretion is poorly understood. Using cancer cells, we identified specialized invasive actin structures called invadopodia as specific and critical docking and secretion sites for CD63- and Rab27a-positive MVEs. Thus, inhibition of invadopodia formation greatly reduced exosome secretion into conditioned media. Functionally, addition of purified exosomes or inhibition of exosome biogenesis or secretion greatly affected multiple invadopodia life cycle steps, including invadopodia formation, stabilization, and exocytosis of proteinases, indicating a key role for exosome cargoes in promoting invasive activity and providing in situ signaling feedback. Exosome secretion also controlled cellular invasion through three-dimensional matrix. These data identify a synergistic interaction between invadopodia biogenesis and exosome secretion and reveal a fundamental role for exosomes in promoting cancer cell invasiveness.

PMID:
24290760
PMCID:
PMC3873329
DOI:
10.1016/j.celrep.2013.10.050
[Indexed for MEDLINE]
Free PMC Article

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