Role of IGF-1R in Mediating Breast Cancer Invasion and Metastasis

Issue title: Insulin Growth Factor

Guest editors: Doug Yee

Article type: Research Article

Authors: Kucab, Jill E. | Dunn, Sandra E.^{; *}

Affiliations: Department of Pediatrics, BC Research Institute for Children's and Women's Health, University of British Columbia, Vancouver BC V6R 2T6, Canada | University of Minnesota, Minneapolis, MN, USA

Correspondence: [*] Corresponding author. 950 W. 28th Ave Vancouver BC V5Z 4H4, Canada. Tel.: +1 604 875 2000 ext 6015; Fax: +1 604 875 3120; E-mail: [email protected]

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 (VEGF165 and VEGF121). 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.

DOI: 10.3233/BD-2003-17105

Journal: Breast Disease, vol. 17, no. 1, pp. 41-47, 2003