fig1

Figure 1. Hyperglycemia promotes cancer growth by regulating thrombospondin (TSP)-1- and TSP-4-dependent pathways. Upregulation of TGF-β in response to hyperglycemia leads to upregulation of TSP-4. TSP-4 is a pro-angiogenic protein that also promotes recruitment of macrophages and other leukocytes into tissues and increases local inflammation. Upregulation of miR-467 in a tissue-specific manner blocks TSP-1 production. In the absence of the anti-angiogenic pressure of TSP-1, cancer angiogenesis is increased. In the absence of TSP-1, the resolution of inflammation is impaired. Increased inflammation and angiogenesis promote cancer growth in the absence of TSP-1. TSP-1 and TSP-4 pathways converge and complement each other to promote the tumor growth