BME Seminar Series: Kelley S. Madden, Ph.D.

Sympathetic Nerves and Norepinephrine in Orthotopic and Spontaneously Occurring Animal Models of Breast Cancer: Function and In Vivo Imaging

Department of Biomedical Engineering, University of Rochester

Abstract

Evidence from breast cancer patients and animal models of breast cancer suggests that stress can facilitate breast tumor growth and metastasis. Activation of the sympathetic nervous system (SNS) and release of norepinephrine (NE) from sympathetic nerves is an important stress pathway. Our goal is to better understand how breast tumor sympathetic nerves and their local release of NE influence tumor growth, angiogenesis, and metastasis.

We have detected sympathetic nerves in the periphery of orthotopic (grown in the mammary fat pad) and spontaneous breast tumors grown in mice. To determine the potential functional interactions between sympathetic nerves, locally released NE, and adrenergic receptor-expressing target cells, we have characterized beta-adrenergic receptor expression in established breast cancer cell lines. Human and mouse breast cancer cell lines express very low to very high levels of beta-adrenergic receptor protein, and this beta-adrenergic receptor heterogeneity has functional significance in vitro. Our current studies are focused on establishing the functional implications of sympathetic activation in vivo. To explore the dynamic effect of catecholamine signaling in breast tumors, we have initiated studies taking advantage of the high resolution capabilities of two photon laser scanning microcopy to image sympathetic nerves within developing tumors in vivo. Ultimately, we hope to determine if sympathetic nerves, NE, or its receptors can be targeted to improve the efficacy of breast cancer therapy.