Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood-brain barrier disturbance but not with patient survival

Abstract

AbstractAquaporin‐4 (AQP4), the most prominent CNS water channel, is restricted to the glia limitans and astrocytic endfeet. We previously showed the loss of spatial AQP4 expression in glioblastomas and a redistribution across the cell surface. However, opposing AQP4 functions have been described: protective in vasogenic but detrimental in cytotoxic brain edema. Thus, specific AQP4 induction to prevent or reduce vasogenic edema is suggested. To elucidate the AQP4 role in brain tumors, we investigated 189 WHO grade I–IV gliomas by immunohistochemistry and the prognostic significance for patients' survival. In gliomas, a remarkable de novo AQP4 redistribution was observed in comparison with normal CNS tissue. Surprisingly, the highest membraneous staining levels were seen in pilocytic astrocytomas WHO grade I and grade IV glioblastomas, both significantly higher than in WHO grade II astrocytomas. AQP4 up‐regulation was associated with brain edema formation; however, no association between survival and WHO grade‐dependent AQP4 expression was seen. Hence, AQP4 redistribution may go along with other tumor properties, such as vascular proliferation and resulting blood–brain barrier disturbance, features usually prominent in pilocytic astrocytomas WHO I and glioblastomas WHO grade IV. In summary, our findings question the protective role of AQP4 in vasogenic brain edema. Although AQP4 was associated with brain edema formation, one has to question the suitability of AQP4 induction as a promising approach in vasogenic brain edema prevention and treatment. In addition, our results provide unexpectedly high AQP4 levels in pilocytic astrocytomas and present AQP4 as tumor progression marker in WHO grade II–IV astrocytomas. © 2007 Wiley‐Liss, Inc.

Autoren

Arne Warth
Perikles Simon
David Capper
Benjamin Goeppert
Ghazaleh Tabatabai
Hajo Herzog
Klaus Dietz
Florian Stubenvoll
Rami Ajaaj
Ralf Becker
Michael Weller
Richard Meyermann
Hartwig Wolburg
Michel Mittelbronn

DOI

10.1002/jnr.21224

eISSN

1097-4547

ISSN

0360-4012

Ausgabe der Veröffentlichung

6

Zeitschrift

Journal of Neuroscience Research

Sprache

en

Online publication date

2007

Paginierung

1336 - 1346

Datum der Veröffentlichung

2007

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1002/jnr.21224

Datum der Datenerfassung

2023

Titel

Expression pattern of the water channel aquaporin‐4 in human gliomas is associated with blood–brain barrier disturbance but not with patient survival

Ausgabe der Zeitschrift

85

Datenquelle: Crossref

Abstract

Aquaporin-4 (AQP4), the most prominent CNS water channel, is restricted to the glia limitans and astrocytic endfeet. We previously showed the loss of spatial AQP4 expression in glioblastomas and a redistribution across the cell surface. However, opposing AQP4 functions have been described: protective in vasogenic but detrimental in cytotoxic brain edema. Thus, specific AQP4 induction to prevent or reduce vasogenic edema is suggested. To elucidate the AQP4 role in brain tumors, we investigated 189 WHO grade I-IV gliomas by immunohistochemistry and the prognostic significance for patients' survival. In gliomas, a remarkable de novo AQP4 redistribution was observed in comparison with normal CNS tissue. Surprisingly, the highest membraneous staining levels were seen in pilocytic astrocytomas WHO grade I and grade IV glioblastomas, both significantly higher than in WHO grade II astrocytomas. AQP4 up-regulation was associated with brain edema formation; however, no association between survival and WHO grade-dependent AQP4 expression was seen. Hence, AQP4 redistribution may go along with other tumor properties, such as vascular proliferation and resulting blood-brain barrier disturbance, features usually prominent in pilocytic astrocytomas WHO I and glioblastomas WHO grade IV. In summary, our findings question the protective role of AQP4 in vasogenic brain edema. Although AQP4 was associated with brain edema formation, one has to question the suitability of AQP4 induction as a promising approach in vasogenic brain edema prevention and treatment. In addition, our results provide unexpectedly high AQP4 levels in pilocytic astrocytomas and present AQP4 as tumor progression marker in WHO grade II-IV astrocytomas.

Addresses

Institute of Pathology, University of Tuebingen, Tuebingen, Germany.

Autoren

Arne Warth
Perikles Simon
David Capper
Benjamin Goeppert
Ghazaleh Tabatabai
Ghazaleh Tabatabai
Hajo Herzog
Klaus Dietz
Florian Stubenvoll
Rami Ajaaj
Ralf Becker
Michael Weller
Richard Meyermann
Hartwig Wolburg
Michel Mittelbronn

DOI

10.1002/jnr.21224

eISSN

1097-4547

Externe Identifier

PubMed Identifier: 17335082

Open access

false

ISSN

0360-4012

Ausgabe der Veröffentlichung

6

Zeitschrift

Journal of neuroscience research

Schlüsselwörter

Blood-Brain Barrier
Brain
Humans
Glioma
Brain Neoplasms
Brain Edema
Disease Progression
Protein Array Analysis
Severity of Illness Index
Multivariate Analysis
Proportional Hazards Models
Sex Factors
Gene Expression Regulation, Neoplastic
Female
Male
Aquaporin 4

Sprache

eng

Medium

Print

Paginierung

1336 - 1346

Datum der Veröffentlichung

2007

Status

Published

Datum der Datenerfassung

2007

Titel

Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood-brain barrier disturbance but not with patient survival.

Sub types

Journal Article

Ausgabe der Zeitschrift

85

Datenquelle: Europe PubMed Central

Abstract

Aquaporin-4 (AQP4), the most prominent CNS water channel, is restricted to the glia limitans and astrocytic endfeet. We previously showed the loss of spatial AQP4 expression in glioblastomas and a redistribution across the cell surface. However, opposing AQP4 functions have been described: protective in vasogenic but detrimental in cytotoxic brain edema. Thus, specific AQP4 induction to prevent or reduce vasogenic edema is suggested. To elucidate the AQP4 role in brain tumors, we investigated 189 WHO grade I-IV gliomas by immunohistochemistry and the prognostic significance for patients' survival. In gliomas, a remarkable de novo AQP4 redistribution was observed in comparison with normal CNS tissue. Surprisingly, the highest membraneous staining levels were seen in pilocytic astrocytomas WHO grade I and grade IV glioblastomas, both significantly higher than in WHO grade II astrocytomas. AQP4 up-regulation was associated with brain edema formation; however, no association between survival and WHO grade-dependent AQP4 expression was seen. Hence, AQP4 redistribution may go along with other tumor properties, such as vascular proliferation and resulting blood-brain barrier disturbance, features usually prominent in pilocytic astrocytomas WHO I and glioblastomas WHO grade IV. In summary, our findings question the protective role of AQP4 in vasogenic brain edema. Although AQP4 was associated with brain edema formation, one has to question the suitability of AQP4 induction as a promising approach in vasogenic brain edema prevention and treatment. In addition, our results provide unexpectedly high AQP4 levels in pilocytic astrocytomas and present AQP4 as tumor progression marker in WHO grade II-IV astrocytomas.

Autoren

Arne Warth
Perikles Simon
David Capper
Benjamin Goeppert
Ghazaleh Tabatabai
Hajo Herzog
Klaus Dietz
Florian Stubenvoll
Rami Ajaaj
Ralf Becker
Michael Weller
Richard Meyermann
Hartwig Wolburg
Michel Mittelbronn

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/17335082

DOI

10.1002/jnr.21224

ISSN

0360-4012

Ausgabe der Veröffentlichung

6

Zeitschrift

J Neurosci Res

Schlüsselwörter

Aquaporin 4
Blood-Brain Barrier
Brain
Brain Edema
Brain Neoplasms
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Glioma
Humans
Male
Multivariate Analysis
Proportional Hazards Models
Protein Array Analysis
Severity of Illness Index
Sex Factors

Sprache

eng

Country

United States

Paginierung

1336 - 1346

Datum der Veröffentlichung

2007

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2007

Titel

Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood-brain barrier disturbance but not with patient survival.

Sub types

Journal Article

Ausgabe der Zeitschrift

85

Datenquelle: PubMed

Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood-brain barrier disturbance but not with patient survival

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