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ResearchIn-Press PreviewAngiogenesisNeuroscience Open Access | 10.1172/jci.insight.143071

Nucleolin promotes angiogenesis and endothelial metabolism along the onco-fetal axis in the human brain vasculature

Marc Schwab,1 Ignazio de Trizio,2 Moheb Ghobrial,3 Jau-Ye Shiu,3 Oguzkan Sürücü,4 Francesco Girolamo,2 Mariella Errede,2 Murat Yilmaz,5 Johannes Haybaeck,6 Alessandro Moiraghi,7 Philippe P. Monnier,8 Sean E. Lawler,9 Jeffrey P. Greenfield,10 Ivan Radovanovic,11 Karl Frei,12 Ralph Schlapbach,13 Viola Vogel,3 Daniela Virgintino,2 Katrien De Bock,14 and Thomas Wälchli15

1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

Find articles by Schwab, M. in: JCI | PubMed | Google Scholar

1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

Find articles by Ghobrial, M. in: JCI | PubMed | Google Scholar

1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

Find articles by Monnier, P. in: JCI | PubMed | Google Scholar |

1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

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1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

Find articles by Virgintino, D. in: JCI | PubMed | Google Scholar |

1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

Find articles by De Bock, K. in: JCI | PubMed | Google Scholar |

1Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland

2Department of Basic Medical Sciences, University of Bari, Bari, Italy

3Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

4Klinik für Psychiatrie und Psychotherapie, Center for Psychiatry Emmendingen, Emmendingen, Switzerland

5Department of Internal Medicine, Cantonal Hospital Lucerne, Lucerne, Switzerland

6Institut of Pathology, Medical University Graz, Graz, Austria

7Department of Clinical Neurosciences, University Hosptial Geneva, Geneva, Switzerland

8Genetics and Development, Toronto Western Research Institute, Toronto, Canada

9Department of Neurosurgery, Brigham and Women's Hospital, Boston, United States of America

10Department of Neurological Surgery, Weill Cornell Medical College, New York, United States of America

11Surgery, University of Toronto, Toronto, Canada

12Department of Neurosurgery, University Hospital Zürich, Zurich, Switzerland

13Functional Genomics Center Zurich, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

14Laboratory of Exercise and Health, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

15University of Toronto, Toronto, Canada

Find articles by Wälchli, T. in: JCI | PubMed | Google Scholar |

Published March 14, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.143071.
Copyright © 2023, Schwab et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 14, 2023 - Version history
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Abstract

Glioblastoma is amongst the deadliest human cancers and is highly vascularized. Angiogenesis is very dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies including brain tumors. The onco-fetal axis describes the reactivation of fetal programs in tumors, but its relevance in endothelial- and perivascular cells of the human brain vasculature in glial brain tumors is unexplored. Nucleolin is a regulator of cell proliferation and angiogenesis, but its roles in the brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit in human fetal brains, adult brains and human gliomas in vivo and its effects on sprouting angiogenesis and endothelial metabolism in vitro. Nucleolin is highly expressed in endothelial- and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression correlated with glioma malignancy in vivo. In culture, siRNA-mediated Nucleolin knock-down reduced human brain endothelial cell (HCMEC) and human umbilical vein endothelial cell (HUVEC) sprouting angiogenesis, proliferation, filopodia extension, and glucose metabolism. Furthermore, inhibition of Nucleolin with the aptamer AS1411 decreased brain endothelial cell proliferation in vitro. Mechanistically, Nucleolin knock-down in HCMECs and HUVECs uncovered regulation of angiogenesis involving VEGFR2 and of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that promotes sprouting angiogenesis and endothelial metabolism, characterizing Nucleolin as an onco-fetal protein. Our findings have potential implications in the therapeutic targeting of glioma.

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