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 journalArticlepeer-review

74 Scopus citations


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
Article numberjcs223321
JournalJournal of Cell Science
Issue number3
StatePublished - 11 Feb 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019. Published by The Company of Biologists Ltd.


This work was supported by National Institutes of Health grants R01 GM071828 to D.C., P01 CA100324 to S.J.H., J.C. and D.C., P01 CA150344 to J.C. and F99 CA212451 (National Cancer Institute) to S.J.H. K.M.-S. was funded under a National Institutes of Health IRACDA fellowship where the content is solely the responsibility of the authors and does not necessarily represent the official views supporting K12GM102779. The 3D-SIM Nikon super resolution microscope used in this study is part of the Analytical Imaging Facility at Albert Einstein College of Medicine supported by National Cancer Institute cancer center grant P30CA013330 and shared instrumentation grant (SIG) 1S10OD18218-1. Deposited in PMC for release after 12 months.

FundersFunder number
National Institutes of HealthP01 CA150344, R01 GM071828, P01 CA100324
National Cancer InstituteK12GM102779, P30CA013330, 1S10OD18218-1, F99CA212451
Pan-Massachusetts Challenge


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


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