Premium
The aquaporin‐1 water channel protein is abnormally expressed in oedematous human brain tumours
Author(s) -
Papadopoulos M. C.,
Saadoun S.,
Krishna S.,
Bell B. A.,
Davies D. C.
Publication year - 2002
Publication title -
journal of anatomy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 118
eISSN - 1469-7580
pISSN - 0021-8782
DOI - 10.1046/j.1469-7580.2002.00047_24.x
Subject(s) - microvessel , pathology , human brain , choroid plexus , astrocytoma , immunoperoxidase , immunocytochemistry , aquaporin 1 , pia mater , biology , astrocyte , ependyma , parenchyma , immunohistochemistry , aquaporin 4 , medicine , central nervous system , glioma , antibody , cancer research , endocrinology , monoclonal antibody , neuroscience , water channel , immunology , mechanical engineering , engineering , inlet
The aquaporins (AQPs) comprise a family of at least 10 highly conserved water channel proteins. Of these only AQP1 and AQP4 are significantly expressed in the brain. In normal brain AQP1 is expressed by the choroid plexus, whereas AQP4 is expressed by astrocyte end‐feet surrounding brain microvessels and forming the glial limiting membrane under the pia mater and ependyma. In order to begin to investigate whether AQP1 is involved in brain water homeostasis, the expression of AQP1 was compared in normal human brain and in human brain tumours where brain water homeostasis is disrupted. Formalin fixed, paraffin embedded samples of morphologically normal human brain ( n = 5), low‐grade (Daumas‐Duport I or II) astrocytomas ( n = 5), high‐grade (Daumas‐Duport III or IV) astrocytomas ( n = 5) and adenocarcinoma metastases to the brain ( n = 5) were obtained from patients who underwent surgery at Atkinson Morley’s Hospital during 1998–9. Astrocytomas and metastatic adenocarcinomas were investigated because they are the commonest human brain tumours. Immunocytochemistry was performed using a polyclonal rabbit anti‐AQP1 primary antibody (AB3065, Chemicon). The immunoreactivity was visualised using immunoperoxidase and diaminobenzidine. In all samples of non‐neoplastic and neoplastic brain, AQP1 immunoreactivity was found over erythrocyte cell membranes. In morphologically normal human brain AQP1 immunolabelling was occasionally observed over microvessel endothelial cells. In 4/5 low grade astrocytomas AQP1 immunolabelling was present over most microvessel endothelial cells and at the periphery of most tumour cells. In all high grade astrocytomas, dense AQP1 immunolabelling was present over most microvessel endothelial cells and both at the periphery and throughout the cytoplasm of most tumour cells. In all metastatic adenocarcinomas AQP1 immunolabelling was present over most microvessel endothelial cells. In 2/5 adenocarcinoma samples AQP1 immunoreactivity was also present in cells with the morphology of reactive astrocytes that were in close proximity to the tumour cells. The presence of AQP1 immunoreactivity in cells within human brain tumours that do not normally express AQP1 and the increasing AQP1 expression with tumour severity, suggest that AQP1 may play a role in the formation of brain tumour oedema. Since brain oedema increases the morbidity and mortality of patients with brain tumours, blocking the AQP1 water channel may provide a way to improve the prognosis of such patients.