Sympathetic nervous system activation, angiogenesis and tumor growth

Women diagnosed with breast cancer experience chronic stress, but the impact of such stress on tumor development is not well understood. We explore the role of an important stress pathway, sympathetic nervous system release of norepinephrine and epinephrine, in tumor growth and metastasis. In vitro studies suggest that these neurotransmitters can promote tumor angiogenesis, the growth of new tumor blood vessels. We have begun to test this possibility in vivo by asking how sympathetic nervous system activation or blockade of norepinephrine and epinephrine alters breast tumor growth and metastasis.

We are also currently exploring the interactions between sympathetic nerve fibers and associated blood vessels within breast tumors. A unique aspect of this project is to determine if sympathetic nerve fibers influence the effectiveness of antiangiogenic therapy. Antiangiogenic therapy shrinks tumors by destroying tumor blood vessels, but stopping therapy elicits rapid tumor revascularization accompanied by aggressive tumor growth. Our studies will elucidate the influence of sympathetic nerve fibers on blood vessel development and function in the growing tumor, and after termination of antiangiogenic therapy. Our goal is to identify new therapeutic targets that improve current antiangiogenic therapies by promoting long-term inhibition of tumor vascularization.

These experiments take advantage of the advanced imaging capabilities of multiphoton laser scanning microscopy (MPLSM) to examine the structural and functional relationships between sympathetic nerves fibers and tumor blood vessels. Ultimately, understanding how a stress pathway influences tumor growth and progression will open the door to therapeutic options targeting the sympathetic nervous system. We hope to use this understanding to develop more effective therapies in breast cancer.

sympathetic nerves

Sympathetic nerves (green) associated with blood vessels (red) in a breast tumor growing in a mammary fat pad of a SCID mouse. Using standard immunofluorescent staining techniques, blood vessels were detected with anti-CD31 and sympathetic noradrenergic nerves were detected with anti-tyrosine hydroxylase. (40X)

tumor vasculature

Tumor vasculature revealed by two photon laser scanning microscopy.

Researcher: Edward Brown III, Ph.D.
Multiphoton Laser Scanning Microscopy, novel in vivo imaging and measurement techniques, tumor biology, angiogenesis