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Journal of Oncology
Volume 2010 (2010), Article ID 539706, 6 pages
Review Article

Sympathetic Neurotransmitters and Tumor Angiogenesis—Link between Stress and Cancer Progression

Department of Physiology & Biophysics, Georgetown University, Basic Science Building 231A, 3900 Reservoir Rd., NW, Washington, DC 20007, USA

Received 16 November 2009; Accepted 18 March 2010

Academic Editor: Sundaram Ramakrishnan

Copyright © 2010 Jason Tilan and Joanna Kitlinska. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recent evidence supports a longstanding hypothesis that chronic stress can influence tumor growth and progression. It has been shown that sympathetic neurotransmitters, such as catecholamines and neuropeptides, can affect both cancer cell growth and tumor vascularization. Depending on neurotransmitter and type of tumor, these effects can be both stimulatory and inhibitory. Norepinephrine (NE) and epinephrine (E) are potent stimulators of vascularization, acting both by inducing the release of angiogenic factors from tumor cells and directly on endothelial cell (EC) functions. As a result, activation of the adrenergic system increases growth of various types of tumors and has been shown to mediate stress-induced augmentation of tumor progression. Dopamine (DA), on the other hand, interferes with VEGF signaling in endothelial cells, blocks its angiogenic functions and inhibits tumor growth. Another sympathetic neurotransmitter coreleased with NE, neuropeptide Y (NPY), directly stimulates angiogenesis. However, proangiogenic actions of NPY can be altered by its direct effect on tumor cell proliferation and survival. In consequence, NPY can either stimulate or inhibit tumor growth, depending on tumor type. Hence, sympathetic neurotransmitters are powerful modulators of tumor growth and can become new targets in cancer therapy.