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 occur 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.
- Received July 30, 2018.
- Accepted December 28, 2018.
- © 2019. Published by The Company of Biologists Ltd
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