Fig. 8.

Model for insulin-like growth factortype 1 receptor (IGF-1R) regulation of primary tumor cellular stress and enhancement of an aggressive tumor microenvironment. Reduced or inhibited IGF-1R function results in increased reactive oxygen species (ROS) accumulation and primary tumor epithelial endoplasmic reticulum (EnR) stress leading to increased production of IL-6 and C-C motif chemokine ligand 2 (CCL2) by the primary tumor epithelium. Secretion of IL-6 and CCL2 signals for monocyte infiltration and differentiation to tumor-associated macrophages (TAM). This differentiation increases MMP expression and secretion resulting in active tumor basement membrane breakdown allowing for increased collagen deposition to provide an environment for tumor cell extravasation