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Figure 2 | Vascular Cell

Figure 2

From: Notch signals in the endothelium and cancer "stem-like" cells: opportunities for cancer therapy

Figure 2

Selected cellular interactions within the CSC niche: Endothelial cells (EC) specialize into "tip" EC, which respond to VEGF-A signals by expressing DLL4 and activating Notch in "stalk" EC, where Notch prevents further branching. Notch-ligand interactions are represented by intercellular receptor-ligand pairs (see inset). Notch-ligand interactions can occur between tip EC and stalk EC, between CC and EC, between CSC and EC. Blood and lymphatic EC contribute to the CSC niche by providing trophic factors and ligand-Notch interactions. Non-stem cancer cells (CC) produce VEGF-A as well as numerous cytokines, including IL-8, IL-6, TNFα, MCP-1, TGF-β and RANTES. VEGF-A activates angiogenesis and has autocrine effects on cancer cells. Some cytokines (e.g., IL-8) act on EC directly, while others (e.g., IL-6, MCP-1) recruit pro-inflammatory Th17 cells. These are stimulated by IL-23 and produce IL-17, which stimulates angiogenesis. TAM produce cytokines (not shown) and VEGF-C. The latter activates VEGFR-3 in EC, stimulating Notch activity and inhibiting further branching in the context of lymphangiogenesis. Additional cells not shown in this diagram include fibroblasts, osteoclasts (in bone metastastases), bone marrow stromal cells, NK cells and others.

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