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Figure 1. Role of the angiogenic factors in iCCA progression. In this schematic Figure 1 (A) we demonstrate the main function exerted by angiogenic factors during iCCA progression. VEGF promotes cancer cell proliferation and metastatic spread, both inhibited by ET-1 and Ang-1. Ang-2 and TSP1, on the other hand, are mainly involved in vascular remodeling during the neoangiogenic process and lymphangiogenesis, respectively, becoming key players in iCCA invasiveness; (B) depicts the complex interplay between angiogenic factors in the CCA microenvironment. Only the most relevant complex exchanges and cellular components characterizing TME are shown in the figure. TAMs: Tumor-associated macrophages; CCA cells: cholangiocarcinoma cells; CAFs: Cancer-associated fibroblasts. The figure was created with Biorender.com