Firstly, they may act directly by binding to the cognate receptor on ECs and thus induce cell proliferation and/or migration (as is the case for VEGF, FGF-2, CXCL-12, angiogenin, IGF-1, progranulin, MMP-9, and Ang-2, in concert with VEGF) or may act on local stromal, immune or tumor cells to influence angiogenic processes indirectly (as is the case for MMP-9, TNF-α, CXCL-12, NGAL, and IGF-1) [1,6,7,9,11,14,15,24,25,26,27,28]. Here, IGF1 is linked to neoplasm.