β 2 -Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer

Chang, Aeson; Le, Caroline P.; Walker, Adam K.; Creed, Sarah J.; Pon, Cindy K.; Albold, Sabine; Carroll, Dominic; Halls, Michelle L.; Lane, J. Robert; Riedel, Bernhard; Ferrari, Davide; Sloan, Erica K.

doi:10.1016/j.bbi.2016.06.011

Cited by 82 publications

(105 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, we determine that the rate of cell proliferation is not altered with isoproterenol or propranolol treatments (Fig. S1G), consistent with our findings for other cancer cell lines (Chang et al, 2016;Kim-Fuchs et al, 2014;Lamkin et al, 2012). Taken together, these findings suggest that the decreased cell deformability induced by isoproterenol treatment is associated with enhanced invasion and migration of cancer cells.…”

Section: Results βAr Signaling Reduces the Deformability Of Cancer Cellssupporting

confidence: 90%

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Kim

Gill

Nyberg

et al. 2016

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Invasion by cancer cells is a crucial step in metastasis. An oversimplified view in the literature is that cancer cells become more deformable as they become more invasive. β-adrenergic receptor (βAR) signaling drives invasion and metastasis, but the effects on cell deformability are not known. Here, we show that activation of β-adrenergic signaling by βAR agonists reduces the deformability of highly metastatic human breast cancer cells, and that these stiffer cells are more invasive in vitro. We find that βAR activation also reduces the deformability of ovarian, prostate, melanoma and leukemia cells. Mechanistically, we show that βAR-mediated cell stiffening depends on the actin cytoskeleton and myosin II activity. These changes in cell deformability can be prevented by pharmacological β-blockade or genetic knockout of the β 2 -adrenergic receptor. Our results identify a β 2 -adrenergicCa 2+ -actin axis as a new regulator of cell deformability, and suggest that the relationship between cell mechanical properties and invasion might be dependent on context.

show abstract

Section: Results βAr Signaling Reduces the Deformability Of Cancer Cellssupporting

confidence: 90%

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Kim

Gill

Nyberg

et al. 2016

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…To investigate this, we treated cells with isoproterenol, a β-adrenergic receptor agonist, and examined cellular metabolite levels using the one-step in-plate method. β-adrenergic receptors are highly expressed by MDA-MB-231 cancer cells and β-adrenergic receptor signalling drives cancer progression [37,38,39]. β-adrenergic receptor activation results in a conformational change to the receptor, which activates G αS and increases cellular levels of cAMP, triggering other intracellular signalling pathways.…”

Section: Resultsmentioning

confidence: 99%

Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells

et al. 2016

View full text Add to dashboard Cite

Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect—an increase in glycolytic activity at the expense of oxidative phosphorylation—and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions.

show abstract

“…49 CAs bind to α1-, α2-, α3-, β1-, β2-, and β3-receptors. Congruently, preclinical evidence implicates β2-adrenoceptors as the major adrenergic signaling pathways in a variety of tumors and immunocytes 49,52,53,[57][58][59][60] ; thus, β2-blockade may be essential in counteracting adrenergic signaling. Congruently, preclinical evidence implicates β2-adrenoceptors as the major adrenergic signaling pathways in a variety of tumors and immunocytes 49,52,53,[57][58][59][60] ; thus, β2-blockade may be essential in counteracting adrenergic signaling.…”

Section: Cas and Pgs: Their Role In Perioperative Sirs And Cancer Biomentioning

confidence: 99%

Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of β‐adrenergic and cyclooxygenase 2 signaling

Ricon

Hanalis-Miller

Haldar

et al. 2018

Cancer

View full text Add to dashboard Cite

Evidence suggests that excess perioperative activation of the sympathetic nervous system and the consequent release of catecholamines (ie, epinephrine and norepinephrine) in the context of cancer surgery and inflammation may significantly facilitate prometastatic processes. This review first presents biomedical processes that make the perioperative timeframe pivotal in determining long-term cancer outcomes nonproportionally to its short duration (days to weeks). Then, it analyzes the various mechanisms via which the excess release of catecholamines can facilitate the progression of cancer metastases in this context by directly affecting the malignant tissues and by regulating, via indirect pathways, immunological and other mechanisms that affect metastatic progression in the tumor microenvironment and systemically. In addition, this review addresses the need to supplement β-adrenoreceptor blockade with cyclooxygenase 2 inhibition, especially during surgery and shortly thereafter, because similar mechanisms are simultaneously activated by surgery-induced inflammatory responses. Importantly, this review presents translational and clinical evidence showing that perioperative β-adrenoreceptor blockade and cyclooxygenase 2 inhibition can reduce the prometastatic process and cancer recurrence, and the clinical feasibility and safety of this approach are demonstrated as well. Lastly, alternative psychophysiological approaches to the use of β-adrenergic blockers are presented because a substantial portion of patients have medical contraindications to this pharmacological treatment. The adaptation of existing psychophysiological interventions to the perioperative period and principles for constructing new approaches are discussed and exemplified. Overall, pharmacobehavioral interventions, separately or in combination, could transform the perioperative timeframe from being a prominent facilitator of metastatic progression to an opportunity for arresting or eliminating residual disease, potentially improving long-term survival rates in cancer patients. Cancer 2019;125:45-56.

show abstract

β 2 -Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer

Cited by 82 publications

References 38 publications

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells

Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of β‐adrenergic and cyclooxygenase 2 signaling

Contact Info

Product

Resources

About