Macrophage-Dependent Cytoplasmic Transfer during Melanoma Invasion In Vivo

Interactions between tumor cells and tumor-associated macrophages play critical roles in the initiation of tumor cell motility. To capture the cellular interactions of the tumor microenvironment with high-resolution imaging, we directly visualized tumor cells and their interactions with macrophages in zebrafish. Live imaging in zebrafish revealed that macrophages are dynamic, yet maintain sustained contact with tumor cells. In addition, the recruitment of macrophages to tumor cells promotes tumor cell dissemination. Using a Cre/LoxP strategy, we found that macrophages transfer cytoplasm to tumor cells in zebrafish and mouse models. Remarkably, macrophage cytoplasmic transfer correlated with melanoma cell dissemination. We further found that macrophages transfer cytoplasm to tumor cells upon cell contact in vitro. Thus, we present a model in which macrophage/tumor cell contact allows for the transfer of cytoplasmic molecules from macrophages to tumor cells corresponding to increased tumor cell motility and dissemination. Roh-Johnson et al. show that macrophages transfer cytoplasmic molecules to tumor cells via cell contact in zebrafish and mouse. Cytoplasmic transfer correlates with increased tumor cell dissemination in vivo and altered tumor cell migration in vitro. These results uncover a mode of contact-dependent cell-to-cell communication in the tumor microenvironment.