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Deletion of endothelial α-parvin inhibits tumour angiogenesis, reduces tumour growth and induces tumour cell apoptosis

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Abstract

Alpha-parvin (α-pv), an adaptor protein that mediates integrin-dependent cell–matrix interactions, is essential for endothelial cells migration and proliferation and is a key player in physiological angiogenesis. The role of α-pv in pathological angiogenesis is unknown. Here we demonstrate that endothelial α-pv is required for tumour angiogenesis. Using an inducible knockout approach in which the α-pv gene (Parva) was inactivated specifically in endothelial cells of brain tumour-bearing mice, we show that loss of endothelial α-pv results in reduced vessel density and decreased vascular complexity of the pathological neo-vasculature without affecting the structure of the brain vasculature around tumour. Reduced tumour vascularisation is associated with a significant increase in tumour cell apoptosis and a reduction in tumour volume. Together, our data show for the first time that endothelial α-pv is required for tumour vascularisation and tumour progression in vivo.

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Acknowledgements

We are grateful for the excellent technical support provided by the Science and Technology Centres of the University of Barcelona at the Bellvitge Campus, by the Core Facility Bioimaging at the Biomedical Center, LMU Munich and by the facility for animal maintenance at the Walter-Brendel-Centre of Experimental Medicine, LMU Munich. REK would like to acknowledge the generous financial support of Dirk Ippen and Marlene Ippen.

Funding

This work has been supported by the Deutsche Forschungsgemeinschaft (MO2562/1–2) and the Spanish Ministry of Science, Innovation and Universities (PID2019-108902 GB-I00). REK and RG are supported by the DFG (GL691/2; SFB824), the „Wilhelm Sander-Stiftung “, the „Anni-Hofmann Stiftung “, and the „Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München “ (WiFoMed).

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  1. Yara Onetti and Roland E. Kälin have contributed equally to this work.

Authors and Affiliations

  1. Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona and Bellvitge Biomedical Research Institute, L’Hospitalet del Llobregat, 08907, Barcelona, Spain

    Yara Onetti, Victor Arribas & Eloi Montanez

  2. Walter Brendel Center of Experimental Medicine, University Hospital, LMU Munich, 81377, Munich, Germany

    Roland E. Kälin, Bettina Pitter, Mengzhuo Hou, Rainer Glass & Eloi Montanez

  3. Neurosurgical Research, University Hospital, LMU Munich, 81377, Munich, Germany

    Roland E. Kälin, Mengzhuo Hou & Rainer Glass

  4. German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Munich, 69120, Heidelberg, Germany

    Rainer Glass

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  1. Yara Onetti
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  2. Roland E. Kälin
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  3. Bettina Pitter
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  4. Mengzhuo Hou
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  7. Eloi Montanez
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Correspondence to Eloi Montanez.

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Onetti, Y., Kälin, R.E., Pitter, B. et al. Deletion of endothelial α-parvin inhibits tumour angiogenesis, reduces tumour growth and induces tumour cell apoptosis. Angiogenesis 25, 155–158 (2022). https://doi.org/10.1007/s10456-021-09829-y

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  • DOI: https://doi.org/10.1007/s10456-021-09829-y

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