Roh-Johnson Minna, Shah Arish N, Stonick Jason A, Poudel Kumud R, Kargl Julia, Yang Grace H, di Martino Julie, Hernandez Rafael E, Gast Charles E, Zarour Luai R, Antoku Susumu, Houghton A McGarry, Bravo-Cordero Jose Javier, Wong Melissa H, Condeelis John, Moens Cecilia B
Fred Hutchinson Cancer Research Center, Basic Sciences Division, Seattle, WA 98109, USA.
Fred Hutchinson Cancer Research Center, Basic Sciences Division, Seattle, WA 98109, USA.
Dev Cell. 2017 Dec 4;43(5):549-562.e6. doi: 10.1016/j.devcel.2017.11.003.
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.
肿瘤细胞与肿瘤相关巨噬细胞之间的相互作用在肿瘤细胞运动的起始过程中起着关键作用。为了通过高分辨率成像捕捉肿瘤微环境的细胞间相互作用，我们在斑马鱼中直接观察肿瘤细胞及其与巨噬细胞的相互作用。斑马鱼活体成像显示，巨噬细胞具有动态性，但与肿瘤细胞保持持续接触。此外，巨噬细胞向肿瘤细胞的募集促进了肿瘤细胞的扩散。利用Cre/LoxP策略，我们发现在斑马鱼和小鼠模型中，巨噬细胞会将细胞质转移到肿瘤细胞。值得注意的是，巨噬细胞的细胞质转移与黑色素瘤细胞的扩散相关。我们进一步发现，在体外细胞接触时，巨噬细胞会将细胞质转移到肿瘤细胞。因此，我们提出了一个模型，即巨噬细胞/肿瘤细胞接触允许细胞质分子从巨噬细胞转移到肿瘤细胞，这与肿瘤细胞运动性和扩散的增加相对应。
