Journal
DEVELOPMENTAL CELL
Volume 43, Issue 5, Pages 549-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2017.11.003
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Funding
- NIH [K99CA190836, T32CA080416, R37 AI054503, K22CA196750, P30 CA196521, R01CA188341, NS082567, R21CA195126]
- FHCRC Cooperative Center for Excellence in Hematology
- AHA [14POST18230006]
- Fondation ARC pour la Recherche sur le Cancer
- European Commission [FP7-PEOPLE-201-IOF 331255]
- OHSU Center for Women's Health Circle of Giving Grant
- Crohn's and Colitis Foundation of America
- Prospect Creek Foundation
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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 microenvironmentwith 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.
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