Fig. 2: Interactions in the fly tumor microenvironment.

Tumor-produced signals alter the surrounding stroma. a) Upregulation of Upd/IL-6 in tumor cells can stimulate proliferation of neighboring WT cells. b) Mispolarization of Sas and Ptp10D at the interface between a tumor clone and WT epithelium promotes death of the tumor cells, triggered by Egr/TNF. The source of Egr/TNF is not yet clear. c) Paracrine Dpp/TGFβ and juxtacrine Delta produced by tumor cells can promote proliferation of underlying mesenchymal myoblasts. d) Bnl/FGF production from hypoxic tumors can attract new tracheal branches. e) Tumor production of MMPs degrades basement membrane and promotes invasion. f) Tumors attract macrophages (dashed arrow) that detect tumor-produced Pvf/VEGF, extracellular ROS and basement membrane damage. Macrophages then upregulate Egr/TNF, which binds to tumor cells and promotes their death.

Figures 1, 2, and 3 were drawn by Nature Reviews Cancer art editor, not the authors of the paper. They can be found in the published version of the paper at DOI: 10.1038/s41568-021-00387-5.