Fig. 3
From: Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer
Five lines of evidence supporting a key role for stroma-derived IGF signaling in PDAC. 1) Stromal cells such as fibroblasts or pancreatic stellate cells (PaSCs) can secrete IGF-1 and enhance the migration capacity of PDAC cells. 2) Proteases such as MMP-3, MMP-7, or MMP-9 that are secreted by stromal cells can cleave IGFBPs and thereby fine-tune IGF activity. 3) Via chemokine secretion, stromal cells can chemo-attract immune cells such as macrophages to the tumor microenvironment and can thereby influence the local tumor control. 4) In a hyperglycaemic state that frequently accompanies PDAC, stromal cells can become activated and cause islet fibrosis and thereby aggravate the hyperglycaemic state. 5) Increasing tissue damage and fibrosis can lead to recruitment of endocrine or exocrine progenitors that can result in transdifferentiation between these cell types