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Activation of multiple angiogenic signaling pathways in hemangiopericytoma

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Abstract

Hemangiopericytoma (HPC) is a highly vascularized mesenchymal tumor. Local recurrence and distant metastasis are common features of HPC. Considering the remarkable hyper-vasculature phenotype of HPC, we assumed that dysregulated angiogenic signaling pathways were involved in HPC. The key components of angiogenic signaling pathways including VEGF–VEGF-R2, EphrinB2-EphB4 and DLL4-Notch were examined by real-time RT-PCR, Western blotting and immunostaining in 17 surgical specimens of HPC patients and in 6 controls. A significant upregulation of VEGF and VEGF-R2 associated with elevated levels of p-Akt and proliferating cell nuclear antigen (PCNA) was detected in HPC. Moreover, a dramatic increase in the mRNA and protein expression of EphB4 and its downstream factor p-Erk1/2 was found in HPC. A massive activation of core-components of DLL4-Notch signaling was detected in HPC. Double-immunofluorescent staining confirmed the expression of these upregulated key factors in the endothelial cells of tumor vessels. The present study identified the activation of multiple and crucial angiogenic signaling pathways, which could function individually and/or synergistically to stimulate angiogenesis in HPC and eventually contribute to tumor growth and progression. Our findings emphasize the importance to target multiple angiogenic signaling pathways when an anti-angiogenic therapy is considered for this highly vascularized tumor.

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Acknowledgments

The authors thank Ms. Rita Haase and Ms. Eva Kusch for technical assistance. The study is financially supported by an IFORES-program from the Medical Faculty, University of Duisburg-Essen to YZ.

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    Authors and Affiliations

    1. Department of Neurosurgery, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany

      Daniela Pierscianek, Anna Michel, Nicolai El Hindy, Philipp Dammann, Neriman Oezkan, Oliver Mueller, Ulrich Sure & Yuan Zhu

    2. Institute of Neuropathology, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany

      Kathy Keyvani

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    1. Daniela Pierscianek
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    Correspondence to Yuan Zhu.

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    D. Pierscianek and A. Michel contributed equally.

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    Pierscianek, D., Michel, A., Hindy, N.E. et al. Activation of multiple angiogenic signaling pathways in hemangiopericytoma. Brain Tumor Pathol 33, 200–208 (2016). https://doi.org/10.1007/s10014-016-0256-6

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    • DOI: https://doi.org/10.1007/s10014-016-0256-6

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