The neurovascular unit in diffuse intrinsic pontine gliomas
Aims: Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a median overall survival of eleven months. Lack of chemotherapy efficacy may be related to an intact blood-brain barrier (BBB). In this study we aim to investigate the neurovascular unit (NVU) in DIPG patients. Met...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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University of Münster / Open Journals System
2021-07-01
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| Series: | Free Neuropathology |
| Subjects: | |
| Online Access: | https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/3341 |
| _version_ | 1819279827644973056 |
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| author | Fatma E. El-Khouly Rianne Haumann Marjolein Breur Sophie E.M. Veldhuijzen van Zanten Gertjan J.L. Kaspers N. Harry Hendrikse Esther Hulleman Dannis G. van Vuurden Marianna Bugiani |
| author_facet | Fatma E. El-Khouly Rianne Haumann Marjolein Breur Sophie E.M. Veldhuijzen van Zanten Gertjan J.L. Kaspers N. Harry Hendrikse Esther Hulleman Dannis G. van Vuurden Marianna Bugiani |
| author_sort | Fatma E. El-Khouly |
| collection | DOAJ |
| description | Aims: Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a median overall survival of eleven months. Lack of chemotherapy efficacy may be related to an intact blood-brain barrier (BBB). In this study we aim to investigate the neurovascular unit (NVU) in DIPG patients.
Methods: DIPG biopsy (n = 4) and autopsy samples (n = 6) and age-matched healthy pons samples (n = 20) were immunohistochemically investigated for plasma protein extravasation, and the expression of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1), basement membrane component laminin, pericyte marker PDGFR-β, and efflux transporters P-gp and BCRP. The mean vascular density and diameter were also assessed.
Results: DIPGs show a heterogeneity in cell morphology and evidence of BBB leakage. Both in tumor biopsy and autopsy samples, expression of claudin-5, ZO-1, laminin, PDGFR-β and P-gp was reduced compared to healthy pontine tissues. In DIPG autopsy samples, vascular density was lower compared to healthy pons. The density of small vessels (<10 µm) was significantly lower (P<0.001), whereas the density of large vessels (≥10 µm) did not differ between groups (P = 0.404). The median vascular diameter was not significantly different: 6.21 µm in DIPG autopsy samples (range 2.25-94.85 µm), and 6.26 µm in controls (range 1.17-264.77 µm).
Conclusion: Our study demonstrates evidence of structural changes in the NVU in DIPG patients, both in biopsy and autopsy samples, as well as a reduced vascular density in end-stage disease. Adding such a biological perspective may help to better direct future treatment choices for DIPG patients. |
| first_indexed | 2024-12-24T00:34:05Z |
| format | Article |
| id | doaj.art-8364693f31c04d428fb0151b61df7ea3 |
| institution | Directory Open Access Journal |
| issn | 2699-4445 |
| language | English |
| last_indexed | 2024-12-24T00:34:05Z |
| publishDate | 2021-07-01 |
| publisher | University of Münster / Open Journals System |
| record_format | Article |
| series | Free Neuropathology |
| spelling | doaj.art-8364693f31c04d428fb0151b61df7ea32022-12-21T17:24:10ZengUniversity of Münster / Open Journals SystemFree Neuropathology2699-44452021-07-01210.17879/freeneuropathology-2021-3341The neurovascular unit in diffuse intrinsic pontine gliomasFatma E. El-Khouly0Rianne Haumann1Marjolein Breur2Sophie E.M. Veldhuijzen van Zanten3Gertjan J.L. Kaspers4N. Harry Hendrikse5Esther Hulleman6Dannis G. van Vuurden7Marianna Bugiani8Emma Children’s Hospital, Amsterdam UMC – location VUmc, Department of Pediatric Oncology, Cancer Center Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The NetherlandsEmma Children’s Hospital, Amsterdam UMC – location VUmc, Department of Pediatric Oncology, Cancer Center Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The NetherlandsAmsterdam UMC – location VUmc, Department of Pathology, de Boelelaan 1117, Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC – location VUmc, Department of Pediatric Oncology, Cancer Center Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The NetherlandsEmma Children’s Hospital, Amsterdam UMC – location VUmc, Department of Pediatric Oncology, Cancer Center Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The NetherlandsAmsterdam UMC – location VUmc, Department of Clinical Pharmacology & Pharmacy, de Boelelaan 1117, Amsterdam, The Netherlands; Amsterdam UMC – location VUmc, Department of Radiology & Nuclear Medicine, de Boelelaan 1117, Amsterdam, The NetherlandsEmma Children’s Hospital, Amsterdam UMC – location VUmc, Department of Pediatric Oncology, Cancer Center Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The NetherlandsEmma Children’s Hospital, Amsterdam UMC – location VUmc, Department of Pediatric Oncology, Cancer Center Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, The NetherlandsAmsterdam UMC – location VUmc, Department of Pathology, de Boelelaan 1117, Amsterdam, The NetherlandsAims: Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a median overall survival of eleven months. Lack of chemotherapy efficacy may be related to an intact blood-brain barrier (BBB). In this study we aim to investigate the neurovascular unit (NVU) in DIPG patients. Methods: DIPG biopsy (n = 4) and autopsy samples (n = 6) and age-matched healthy pons samples (n = 20) were immunohistochemically investigated for plasma protein extravasation, and the expression of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1), basement membrane component laminin, pericyte marker PDGFR-β, and efflux transporters P-gp and BCRP. The mean vascular density and diameter were also assessed. Results: DIPGs show a heterogeneity in cell morphology and evidence of BBB leakage. Both in tumor biopsy and autopsy samples, expression of claudin-5, ZO-1, laminin, PDGFR-β and P-gp was reduced compared to healthy pontine tissues. In DIPG autopsy samples, vascular density was lower compared to healthy pons. The density of small vessels (<10 µm) was significantly lower (P<0.001), whereas the density of large vessels (≥10 µm) did not differ between groups (P = 0.404). The median vascular diameter was not significantly different: 6.21 µm in DIPG autopsy samples (range 2.25-94.85 µm), and 6.26 µm in controls (range 1.17-264.77 µm). Conclusion: Our study demonstrates evidence of structural changes in the NVU in DIPG patients, both in biopsy and autopsy samples, as well as a reduced vascular density in end-stage disease. Adding such a biological perspective may help to better direct future treatment choices for DIPG patients.https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/3341Diffuse intrinsic pontine glioma (DIPG)Neurovascular unit (NVU)Blood-brain barrier (BBB)Tight junctionsBrainstemPons |
| spellingShingle | Fatma E. El-Khouly Rianne Haumann Marjolein Breur Sophie E.M. Veldhuijzen van Zanten Gertjan J.L. Kaspers N. Harry Hendrikse Esther Hulleman Dannis G. van Vuurden Marianna Bugiani The neurovascular unit in diffuse intrinsic pontine gliomas Free Neuropathology Diffuse intrinsic pontine glioma (DIPG) Neurovascular unit (NVU) Blood-brain barrier (BBB) Tight junctions Brainstem Pons |
| title | The neurovascular unit in diffuse intrinsic pontine gliomas |
| title_full | The neurovascular unit in diffuse intrinsic pontine gliomas |
| title_fullStr | The neurovascular unit in diffuse intrinsic pontine gliomas |
| title_full_unstemmed | The neurovascular unit in diffuse intrinsic pontine gliomas |
| title_short | The neurovascular unit in diffuse intrinsic pontine gliomas |
| title_sort | neurovascular unit in diffuse intrinsic pontine gliomas |
| topic | Diffuse intrinsic pontine glioma (DIPG) Neurovascular unit (NVU) Blood-brain barrier (BBB) Tight junctions Brainstem Pons |
| url | https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/3341 |
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