Tunneling nanotubes, a novel mode of tumor cell-macrophage communication in tumor cell invasion

Samer J. Hanna, Kessler McCoy-Simandle, Edison Leung, Alessandro Genna, John Condeelis, Dianne Cox

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The interaction between tumor cells and macrophages is crucial in promoting tumor invasion and metastasis. In this study, we examined a novel mechanism of intercellular communication, namely membranous actin-based tunneling nanotubes (TNTs), that occurs between macrophages and tumor cells in the promotion of macrophage-dependent tumor cell invasion. The presence of heterotypic TNTs between macrophages and tumor cells induced invasive tumor cell morphology, which was dependent on EGF-EGFR signaling. Furthermore, reduction of a protein involved in TNT formation, M-Sec (TNFAIP2), in macrophages inhibited tumor cell elongation, blocked the ability of tumor cells to invade in 3D and reduced macrophage-dependent long-distance tumor cell streaming in vitro Using an in vivo zebrafish model that recreates macrophage-mediated tumor cell invasion, we observed TNT-mediated macrophage-dependent tumor cell invasion, distant metastatic foci and areas of metastatic spread. Overall, our studies support a role for TNTs as a novel means of interaction between tumor cells and macrophages that leads to tumor progression and metastasis.

Original languageEnglish (US)
JournalJournal of cell science
Volume132
Issue number3
DOIs
StatePublished - Feb 11 2019

Keywords

  • Cell communication
  • Invasion
  • Macrophages
  • Tumor cell streaming
  • Tunneling nanotubes

ASJC Scopus subject areas

  • Cell Biology

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