Volume 14 Supplement 1

6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access

A novel role of the natriuretic peptide/cGMP/cGKI pathway in melanoma cells

  • Sandeep Dhayade1Email author,
  • Susanne Feil1,
  • Christoph Griessinger2,
  • Manfred Kneilling3,
  • Birgit Schittek3 and
  • Robert Feil1
BMC Pharmacology and Toxicology201314(Suppl 1):P19

DOI: 10.1186/2050-6511-14-S1-P19

Published: 29 August 2013

Background

The cGMP/cGMP-dependent protein kinase type I (cGKI) signaling pathway is activated by nitric oxide (NO), natriuretic peptides (ANP, BNP & CNP), and cGMP-elevating drugs. It regulates important physiological functions such as platelet aggregation, smooth muscle tonus, and cell growth and survival. Recent reports indicate that cGMP might also play a role in tumorigenesis. In the present study we found that cGKI is expressed in melanoma cells of murine and human origin.

Results

Treatment of intact mouse B16 melanoma cells with the membrane-permeable cGMP analog 8-Br-cGMP induced phosphorylation of the cGKI substrates, vasodilator-stimulated phosphoprotein and phosphodiesterase 5. ANP and CNP, ligands of the membrane-bound guanylyl cyclase GC-A and GC-B, respectively, activated the endogenous cGMP/cGKI pathway. CNP-induced cGMP signals were detected in cell extracts by ELISA and in living cells by a FRET-based cGMP sensor [1]. DEA/NO, which stimulates NO-sensitive soluble guanylyl cyclase, did not increase cGMP signaling in B16 cells. Interestingly, activation of cGMP/cGKI signal transduction was associated with an increase in ERK1/2 and p38 phosphorylation, growth and migration of B16 melanoma cells. Similar results were obtained with WM1205 human melanoma cells.

Conclusion

We have identified a natriuretic peptide/cGMP/cGKI pathway in melanoma cells, which stimulates tumor cell growth and migration in vitro. Pharmacologic inhibition of cGMP signaling may offer a promising strategy for the treatment of melanoma.

Authors’ Affiliations

(1)
Interfakultäres Institut für Biochemie, University of Tübingen
(2)
Department of Preclinical Imaging and Radiopharmacy, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, University of Tübingen
(3)
Department of Dermatology, University of Tübingen

References

  1. Russwurm M, Mullershausen F, Friebe A, Jager R, Russwurm C, Koesling D: Design of fluorescence resonance energy transfer (FRET)-based cGMP indicators: a systematic approach. Biochem J. 2007, 407: 69-77. 10.1042/BJ20070348.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Dhayade et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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