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Typically, the tumor microenvironment is a stroma-like tissue with altered ECM components, newly formed blood vessels, infiltrating macrophages called tumor-associated macrophages (TAMs), and numerous cancer-affected fibroblasts called cancer-associated fibroblasts (CAF), which crosstalk with malignant cells to support tumorigenesis and are responsible for matrix remodeling ( 2.2 Insulin-like peptides and receptors Insulin-like peptides (ILPs), which include IGF-1, IGF-2, insulin, and seven relaxin-related peptides sharing the same basal fold in humans, are evolutionary conserved factors that play a central role in the regulation of energy metabolism, cell growth and proliferation, and neurotransmission ( ILP receptors include the IGF-2 receptor (IGF-2R) that clears IGF-2 from the cell surface without signal transduction and structurally related receptor tyrosine kinases, namely: insulin receptor isoform A (IR-A), which has a strong affinity for insulin and IGFs, and is involved in cell growth, proliferation and survival
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