β2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion
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Creed, Sarah J, et al. Β2-adrenoceptor Signaling Regulates Invadopodia Formation to Enhance Tumor Cell Invasion. BioMed Central, 2015. https://doi.org/10.17615/pf6g-yx60APA
Creed, S., Le, C., Hassan, M., Pon, C., Albold, S., Chan, K., Berginski, M., Huang, Z., Bear, J., Lane, J., Halls, M., Ferrari, D., Nowell, C., & Sloan, E. (2015). β2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion. BioMed Central. https://doi.org/10.17615/pf6g-yx60Chicago
Creed, Sarah J, Caroline P Le, Mona Hassan, Cindy K Pon, Sabine Albold, Keefe T Chan, Matthew E Berginski et al. 2015. Β2-Adrenoceptor Signaling Regulates Invadopodia Formation to Enhance Tumor Cell Invasion. BioMed Central. https://doi.org/10.17615/pf6g-yx60- Alternate title
- [Beta]2-adrenoceptor signaling regulates invadopodia formation to enhance tumor cell invasion
- Creator
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Creed, Sarah J
- Other Affiliation: Monash University
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Le, Caroline P
- Other Affiliation: Monash University
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Hassan, Mona
- Other Affiliation: Monash University
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Pon, Cindy K
- Other Affiliation: Monash University
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Albold, Sabine
- Other Affiliation: Monash University
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Chan, Keefe T
- Affiliation: School of Medicine, Department of Cell Biology and Physiology
- Other Affiliation: Peter MacCallum Cancer Centre
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Berginski, Matthew E
- Other Affiliation: Duke University
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Huang, Zhendong
- Other Affiliation: The University of Melbourne
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Bear, James
- Affiliation: School of Medicine, Department of Cell Biology and Physiology
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Lane, J. Robert
- Other Affiliation: Monash University
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Halls, Michelle L
- Other Affiliation: Monash University
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Ferrari, Davide
- Other Affiliation: The University of Melbourne
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Nowell, Cameron J
- Other Affiliation: Monash University
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Sloan, Erica K
- Other Affiliation: Monash University
- 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.
- Date of publication
- November 25, 2015
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Creed et al.
- Journal title
- Breast Cancer Research
- Journal volume
- 17
- Journal issue
- 1
- Page start
- 145
- Language
- English
- Bibliographic citation
- Breast Cancer Research. 2015 Nov 25;17(1):145
- Publisher
- BioMed Central
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