Tumor-stromal interactions promoted either single cell or collective cell invasion. Combinatorial xenografts of either enhanced GFP-labeled transforming growth factor-beta receptor II control (TβRIIfl/fl) or transforming growth factor-beta receptor II knockout (TβRII KO) carcinoma cells with fibroblasts (fib) were grafted onto the chorioallantoic membrane and monitored via intravital imaging. (A) Top panel, single cell migration was exhibited in tumors that maintain epithelial transforming growth factor-beta (TGF-β) signaling. Only the epithelial channel is shown in order to visualize the single cell and strands displayed. Bottom panel, collective migration was observed in TβRII KO tumors (arrow). Both epithelial (green) and fibroblast (red) channels are overlayed. Fibroblasts guided both types of epithelial migration. (B) Migration types observed when comparing TβRIIfl/fl control and TβRII KO ex ovo tumors are quantified. (C) TβRII KO tumors migrated collectively along and around the vasculature, as shown by two-photon microscopy. Vasculature (left), epithelial (middle), and overlayed (right) panels are shown. The fibroblasts were unlabeled and therefore not shown. (D) Fibroblasts had enhanced velocity in the presence of TβRII KO epithelial cells compared with TβRIIfl/fl cells.