Augmentation of Breast Cancer Growth and Metastasis by Chronic Stressor Exposure
Abstract
Exposure to stress has been shown to increase tumor growth in a number of animal models in association with greater tumor angiogenesis and elevated vascular endothelial growth factor (VEGF), an important initiator of angiogenesis and tumor progression. Similarly, tumor cell lines in vitro are susceptible to -adrenergic receptor ( -AR)-mediated elevation of VEGF and other proangiogenic and prometastatic factors, such as interleukin-6 (IL-6) and matrix metalloproteinases (MMP). Together, these results suggest that stress-induced activation of the sympathetic nervous system and norepinephrine (NE) release stimulates tumor cell - AR to promote tumor growth at least in part by facilitating tumor angiogenesis. We previously determined that MDA-MB-231 (MB-231), a human breast cancer cell line that represents the more aggressive triple negative phenotype, expresses many -AR sites per tumor cell. By comparison, 4T1, a murine mammary adenocarcinoma cell line, expresses no detectable -AR surface expression or signaling. To investigate a role for sympathetic nervous system involvement via -AR stimulation in breast cancer pathogenesis in vivo, we have assessed sympathetic tyrosine-hydroxylase-positive (TH+) innervation of MB-231 and 4T1 tumors grown orthotopically (in the mammary fat pad). Furthermore, we investigated the impact of sympathetic activation on in vivo tumor growth of MB-231 and 4T1 tumors using two approaches to activate the sympathetic nervous system: 1) social isolation, a chronic stressor that has been shown to facilitate ovarian tumor growth; and 2) chronic desipramine treatment (a tricyclic antidepressant used clinically that inhibits NE reuptake).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA553339
Entities
People
- Mercedes J. Szpunar
Organizations
- University of Rochester