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Protein kinase CK2 is a regulator of angiogenesis in endometriotic lesions

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Abstract

Endometriosis is a frequent gynecological disease, which is crucially dependent on the process of angiogenesis. However, the underlying regulatory mechanisms of blood vessel development are still poorly understood. CK2 is a pleiotropic protein kinase, which is implicated in the regulation of various cellular processes including angiogenesis. Herein we studied for the first time the function of protein kinase CK2 in angiogenesis of endometriotic lesions. For this purpose, we analyzed the anti-angiogenic activity of the CK2 inhibitor quinalizarin in a rat aortic ring assay and its effect on the expression of individual CK2 subunits and on kinase activity in endometrial tissue. Moreover, endometriotic lesions were induced in dorsal skinfold chambers of quinalizarin- and vehicle-treated C57BL/6 mice to study their vascularization and morphology by means of repetitive intravital fluorescence microscopy and histology. Our results demonstrate that quinalizarin dose-dependently inhibits vascular sprouting. In addition, treatment of endometrial tissue with quinalizarin reduces CK2 activity without affecting the expression of the three CK2 subunits α, α′ and β. In the dorsal skinfold chamber model of endometriosis, quinalizarin inhibits the vascularization of endometriotic lesions, which exhibit a significantly decreased vascularized area and functional capillary density when compared to those of vehicle-treated controls. This is associated with a reduced lesion size and histological fraction of endometrial glands. These findings indicate that CK2 is a regulator of angiogenesis in endometriotic lesions. Accordingly, inhibition of CK2 represents a novel option in the development of anti-angiogenic strategies for the treatment of endometriosis.

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Acknowledgments

We are grateful for the excellent technical assistance of Janine Becker from the Institute of Clinical and Experimental Surgery, Homburg/Saar, Germany.

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The authors declare that they have no conflict of interest.

Ethical standards

All experiments of this study comply with the current laws of Germany. They were approved by the local governmental animal care committee and were conducted in accordance with the German legislation on protection of animals and the NIH Guidelines for the Care and Use of Laboratory Animals (NIH Publication #85-23 Rev. 1985).

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Correspondence to Matthias W. Laschke.

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Feng, D., Welker, S., Körbel, C. et al. Protein kinase CK2 is a regulator of angiogenesis in endometriotic lesions. Angiogenesis 15, 243–252 (2012). https://doi.org/10.1007/s10456-012-9256-2

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