Norepinephrine inhibits the migratory activity of pancreatic cancer cells.

Anna-Maria Stock, Desmond G Powe, Stephan A Hahn, Gabriele Troost, Bernd Niggemann, Kurt S Zänker, Frank Entschladen

Institute of Immunology and Experimental Oncology, Centre for Biomedical Education and Research ZBAF, Witten/Herdecke University, 58448 Witten, Germany.

Experimental cell research 2013 Jul 15

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We have shown previously that norepinephrine induces migratory activity of tumour cells from breast, colon and prostate tissue via activation of beta-2 adrenergic receptors. Consequently, this effect can be inhibited pharmacologically by clinically established beta-blockers. Tumour cell migration is a prerequisite for metastasis formation, and accordingly we and others have shown that breast cancer patients, which take beta-blockers due to hypertension, have reduced metastasis formation and increased survival probability as compared to patients without hypertension or using other anti-hypertensive medication. Unlike the aforementioned tumour cells, pancreatic cancer cells show a reduced migratory activity upon norepinephrine treatment. By means of our three-dimensional, collagen-based cell migration assay, we have investigated the signal transduction pathways involved in this phenomenon. We have found that this conflicting effect of norepinephrine on pancreatic cancer cells is due to an imbalanced activation of the two pathways that usually mediate a pro-migratory effect of norepinephrine in other tumour cell types. Firstly, the inhibitory effect results from activation of a pathway which causes a strong increase of the secondary cell signalling molecule, cAMP. In addition, activation of phospholipase C gamma and the downstream protein kinase C alpha were shown to be already activated in pancreatic cancer cells and cannot be further activated by norepinephrine. We hypothesize that this constitutive activation of the phospholipase C gamma pathway is due to a cross-talk with receptor tyrosine kinase signalling, and this might also deliver an explanation for the unusual high spontaneous migratory activity of pancreatic cancer cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Anna-Maria Stock, Desmond G Powe, Stephan A Hahn, Gabriele Troost, Bernd Niggemann, Kurt S Zänker, Frank Entschladen. Norepinephrine inhibits the migratory activity of pancreatic cancer cells. Experimental cell research. 2013 Jul 15;319(12):1744-58