IGF1 and cancer: Studies on IGF system in normal epithelial and cancerous cells such as those of the breast have found that IGF-IR is activated in one of two ways through IGF-I: (1) hepatic production of IGF-I can increase serum IGF-I, which in turn may act in an autocrine manner as a stimulatory molecule to induce the proliferation of normal as well as cancer cells; and/or (2) local production of IGF-I by stromal cells that surround the tumorigenic cells serves as a paracrine stimulator of the IGF-IR signaling [48, 49].