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Accession Number:
ADA516637
Title:
Neural Regulation of Breast Cancer Metastasis
Descriptive Note:
Final rept. 15 Sep 2008-17 Sep 2009
Corporate Author:
CALIFORNIA UNIV LOS ANGELES
Report Date:
2009-10-01
Pagination or Media Count:
13.0
Abstract:
Metastasis to distant organs is responsible for much of the morbidity and mortality of breast cancer. Recent research has focused on the host microenvironment as a target for new anti-cancer therapies 1, 2. This research has shown that mUltiple host cell types contribute to tumor metastasis. However, little attention has focused on the neural component of the tumor microenvironment. Nerve fibers from the sympathetic branch of the autonomic nervous system innervate organs that are preferentially targeted by breast cancer metastasis, including lymph nodes, lungs, and bone 3-5. By modulating the microenvironment targeted by metastasis, it is possible that the host sympathetic nervous system SNS may contribute to breast cancer metastasis in the presence of chronic stress. Chronic stress can increase the density of SNS nerve fibers in lymph nodes by through the neurotrophic actions of Nerve Growth Factor 6. This provides an anatomical basis for increased SNS signaling in this metastatic target tissue during periods of chronic stress. Furthermore, -adrenergic receptors have been documented in multiple tumor types, including breast cancer 7-9. In vitro studies have shown that SNS signaling regulates multiple pathways that converge on the metastatic phenotype, inclUding tumor cell proliferation, invasion, angiogenesis, matrix metalloprotease activation, src oncogene signaling, and expression of interleukins-6 and -8 10-12.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
