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Cancer cells and inflammatory cells in the tumor microenvironment secrete lymphangiogenic factors, such as VEGF-C (65, 66), VEGF-D (67), PDGF-BB (69), IGF-1 and IGF-2 (75), HGF (76, 77), FGF-2 (78), interleukin-1 (79), and COX-2 (80), promoting the proliferation and dilatation of peritumoral lymphatics, thereby favoring their metastatic spread ( Figure 1 )