Immune function, including the emerging field of immuno-oncology, and cancer metastasis depend on cells’ ability to move through tissue barriers. We utilize the developmental migration of Drosophila melanogaster macrophages as they penetrate the extended germband to reveal what cellular shifts are required in invading cells and invaded tissues. We have recently identified two stories I will talk about. We have found through two color live imaging that what determines the capacity of initial macrophage infiltration is actually the division of the surrounding cells. This provides a powerful new perspective on this process. We have shown that division disassembles the focal adhesions that anchor ectodermal cells to the surrounding ECM, removing a steric hindrance for macrophages to enter. In collaborative work with the Clevers lab and the Munro lab, we have shown that cell division also regulates the entry of vertebrate monocytes and neutrophils, underscoring the power of the fly system to identify broadly applicable principles for invasion. Our work raises the possiblity that macrophages might induce their own invasion, by triggering division.
In other work in collaboration with the Giangrande and Cochella labs, we have identified that BMP signaling from the surroundings specifies the pathway that specifies a pioneer leader macrophage which enables effective infiltration. This induction by an external signal of a distinct transcriptional program in a subset of migrating cells allows them to adopt a distinct spatial position during invasion and enhance its efficiency.
Our system thus provides excellent opportunities to model how stochastic versus developmentally programmed changes in the environment and the migrating cell itself affect the invasive behavior of an immune cell.