Sarah J Creed
β2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion
Creed, Sarah J; Le, Caroline P; Hassan, Mona; Pon, Cindy K; Albold, Sabine; Chan, Keefe T; Berginski, Matthew E; Huang, Zhendong; Bear, James E; Lane, J Robert; Halls, Michelle L; Ferrari, Davide; Nowell, Cameron J; Sloan, Erica K
Authors
Caroline P Le
Mona Hassan
Cindy K Pon
Sabine Albold
Keefe T Chan
Matthew E Berginski
Zhendong Huang
James E Bear
ROB LANE ROB.LANE@NOTTINGHAM.AC.UK
Associate Professor
Michelle L Halls
Davide Ferrari
Cameron J Nowell
Erica K Sloan
Abstract
INTRODUCTION:For efficient metastatic dissemination, tumor cells form invadopodia to degrade and move through three-dimensional extracellular matrix. However, little is known about the conditions that favor invadopodia formation. Here, we investigated the effect of β-adrenoceptor signaling - which allows cells to respond to stress neurotransmitters - on the formation of invadopodia and examined the effect on tumor cell invasion. METHODS:To characterize the molecular and cellular mechanisms of β-adrenergic signaling on the invasive properties of breast cancer cells, we used functional cellular assays to quantify invadopodia formation and to evaluate cell invasion in two-dimensional and three-dimensional environments. The functional significance of β-adrenergic regulation of invadopodia was investigated in an orthotopic mouse model of spontaneous breast cancer metastasis. RESULTS:β-adrenoceptor activation increased the frequency of invadopodia-positive tumor cells and the number of invadopodia per cell. The effects were selectively mediated by the β2-adrenoceptor subtype, which signaled through the canonical Src pathway to regulate invadopodia formation. Increased invadopodia occurred at the expense of focal adhesion formation, resulting in a switch to increased tumor cell invasion through three-dimensional extracellular matrix. β2-adrenoceptor signaling increased invasion of tumor cells from explanted primary tumors through surrounding extracellular matrix, suggesting a possible mechanism for the observed increased spontaneous tumor cell dissemination in vivo. Selective antagonism of β2-adrenoceptors blocked invadopodia formation, suggesting a pharmacological strategy to prevent tumor cell dissemination. CONCLUSION:These findings provide insight into conditions that control tumor cell invasion by identifying signaling through β2-adrenoceptors as a regulator of invadopodia formation. These findings suggest novel pharmacological strategies for intervention, by using β-blockers to target β2-adrenoceptors to limit tumor cell dissemination and metastasis.
Citation
Creed, S. J., Le, C. P., Hassan, M., Pon, C. K., Albold, S., Chan, K. T., …Sloan, E. K. (2015). β2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion. Breast Cancer Research, 17(1), Article 145. https://doi.org/10.1186/s13058-015-0655-3
Journal Article Type | Article |
---|---|
Acceptance Date | Nov 9, 2015 |
Online Publication Date | Nov 25, 2015 |
Publication Date | Nov 25, 2015 |
Deposit Date | Apr 22, 2020 |
Publicly Available Date | May 4, 2020 |
Journal | Breast Cancer Research |
Print ISSN | 1465-5411 |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 17 |
Issue | 1 |
Article Number | 145 |
DOI | https://doi.org/10.1186/s13058-015-0655-3 |
Public URL | http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26607426&retmode=ref&cmd=prlinks |
Publisher URL | https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0655-3 |
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Publisher Licence URL
https://creativecommons.org/licenses/by/2.0/
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