Abstract B092: Beta-blockade of breast cancer metastasis: Receptor regulation and downstream signaling pathways
| Autor: | David M. Shackleford, Andreas Moeller, Matthew A. Pimentel, Sarah J. Creed, Izhak Haviv, Caroline P. Le, Ming Gene Chai, Erica K. Sloan, J. Robert Lane, Benjamin Arthur Llewellyn Finnin |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Molecular Cancer Research. 11:B092-B092 |
| ISSN: | 1557-3125 1541-7786 |
| Popis: | Chronic stress accelerates breast cancer metastasis through beta-adrenergic signaling and recent clinical studies found that beta-blockade reduced metastasis in women with breast cancer. However, the specific beta-adrenergic receptor subtype(s) through which stress-responsive neurotransmitters mediates effects on cancer remain unknown. To identify the receptor that transmits beta-adrenergic signaling to primary mammary tumors, we used bioluminescence imaging to longitudinally quantify the effect on metastasis of beta-blockers that selectively inhibit beta1 vs. beta 2 adrenergic receptors in an orthotopic mouse model of breast cancer progression. Non-specific beta-blockade with propranolol reduced metastasis by >90% (p = .03), confirming a key role for beta-adrenergic signaling pathways in stress-enhanced metastasis. Treatment with the beta2-selective antagonist ICI118551 similarly reduced stress-enhanced metastasis to control levels. In contrast, beta-1 selective blockade failed to protect against metastasis. Pharmacological intervention studies and gene expression analyses have started to define the downstream signaling pathways of beta-adrenergic regulation of metastasis. These studies may provide mechanistic explanation for recent clinical findings that not all beta-blockers protect against metastasis and provide a framework for selection of cancer patients who may optimally benefit from beta-blockade. Citation Format: Ming Gene Chai, Caroline P. Le, Sarah J. Creed, Benjamin A L Finnin, Matthew A. Pimentel, David Shackleford, Andreas Moeller, Izhak Haviv, J. Robert Lane, Erica K. Sloan. Beta-blockade of breast cancer metastasis: Receptor regulation and downstream signaling pathways. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B092. |
| Databáze: | OpenAIRE |
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