title: Role of IGF-1R in mediating breast cancer invasion and metastasis.
abstract: In this review we bring forward what is currently known about the role of type I insulin-like growth factor receptor (IGF-1R) in mediating breast cancer invasion and metastasis. We begin by addressing how activated IGF-1R could allow pre-cancerous cells to become invasive. To this effect, we discuss clinical reports suggesting that activation of IGF-1R could stimulate ductal carcinoma in situs to become invasive. In the same light, we review basic research from our laboratory showing that IGF-1R differentially regulates the expression of breast cancer progression genes when pre-malignant breast epithelial cells were stimulated with insulin-like growth factor-I (IGF-I) over time. The discussion then turns toward the ability of IGF-1R to stimulate invasion of breast cancer cells that have acquired a malignant phenotype. At this stage of breast cancer, it appears that IGF-I stimulates cells to invade in part by inducing urokinase plasminogen activator. Finally, we consider the potential role of IGF-1R in regulating breast cancer metastases by facilitating angiogenesis and lymphangiogenesis. In support of this idea, there is evidence for IGF-1R in both of these processes through the induction of vascular endothelial growth factors (VEGF(165) and VEGF(121)). Thus, IGF-1R affords breast cancer cells many opportunities to become invasive and eventually metastatic. We conclude that disrupting IGF-1R signaling has many important implications in the treatment and management of breast cancer.
authors.affiliation: Department of Pediatrics, BC Research Institute for Children's and Women's Health, University of British Columbia, Vancouver BC V6R 2T6, Canada.
authors.forename: Jill E
authors.initials: JE
authors.lastname: Kucab
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Dunn