Augmentation of Breast Cancer Growth and Metastasis by Chronic Stressor Exposure
Abstract
Cancer patients often experience chronic emotional stress with diagnosis and successive treatment. Psychosocial stressors can activate the sympathetic nervous system (SNS) to release the catecholamine norepinephrine (NE), which can stimulate alpha- and beta-adrenergic receptors (alpha- and beta-AR). AR stimulation by NE or other agonists has been shown to influence tumor growth in vitro and in vivo through induction of angiogenesis and/or metastasis. Our laboratory studies tumor collagen structure through an optical technique called second harmonic generation (SHG). Changes in collagen structure, as manifested by changes in SHG, can alter tumor growth and metastasis. Our objective is to delineate the role of NE and AR stimulation in breast cancer growth and metastasis in the 4T1 murine tumor model. To mimic SNS activation, female BALB/c mice were implanted with slow-release pellets containing desipramine (DMI) a tricyclic antidepressant that prevents NE reuptake from noradrenergic synapses. DMI treatment increased 4T1 primary tumor growth, but the DMI-induced growth was not associated with altered tumor vasculature or metastasis. However, tumor sections from DMI-implanted mice exhibited altered SHG intensity, demonstrating changes in tumor collagen structure. Tumor growth and metastasis were increased in mice treated with dexmedetomidine (DEX), a highly selective 2-AR agonist, but not isoproterenol ( -AR agonist) or phenylephrine ( 1-AR agonist). The DEX-induced alterations in tumor progression were also associated with alterations in collagen structure as measured by SHG. These results reveal an undescribed role for 2-AR in tumor progression, and suggest a novel pathway by which elevated NE may promote tumor progression through the extracellular matrix.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA589201
Entities
People
- Mercedes Szpunar
Organizations
- University of Rochester