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Water Channels Aquaporin 4 and -1 Expression in Subependymoma Depends on the Localization of the Tumors.

Noell S, Fallier-Becker P, Mack AF, Hoffmeister M, Beschorner R, Ritz R - PLoS ONE (2015)

Bottom Line: In contrast, aquaporin 1 RNA levels were found to be higher only in infratentorial samples compared to supratentorial and normal brain samples.On the cellular level, aquaporin 4 was redistributed on the surface of the tumor cells, and in freeze fracture replicas no orthogonal arrays of particles were found.This was similar to our previous findings in malignant glioblastomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, University of Tuebingen, Tuebingen, Germany.

ABSTRACT

Background: We analyzed aquaporin 4 and -1 expression in subependymomas, benign and slow growing brain tumors WHO grade I. Ten subependymoma cases were investigated, five of the fossa inferior and five of the fossa superior.

Methods and results: Using immunohistochemistry, we observed different aquaporin expression patterns depending on localization: aquaporin 4 and -1 were detected in infratentorial subependymomas in the entire tumor tissue. In contrast, supratentorial subependymomas revealed aquaporin 4 and -1 expression only in border areas of the tumor. PCR analyses however showed no difference in aquaporin 4 expression between all subependymomas independent of localization but at higher levels than in normal brain. In contrast, aquaporin 1 RNA levels were found to be higher only in infratentorial samples compared to supratentorial and normal brain samples. The reason for the different distribution pattern of aquaporin 4 in subependymomas still remains unclear. On the cellular level, aquaporin 4 was redistributed on the surface of the tumor cells, and in freeze fracture replicas no orthogonal arrays of particles were found. This was similar to our previous findings in malignant glioblastomas. From these studies, we know that extracellular matrix molecules within the tumor like agrin and its receptor alpha-dystroglycan are involved in forming orthogonal arrays of particles. In subependymomas neither agrin nor alpha-dystroglycan were detected around blood vessels.

Conclusions: Taken together, we show in this study that in the benign subependymomas aquaporins 1 and 4 are dramatically redistributed and upregulated. We speculate that extracellular environments of infra- and supratentorial subependymomas are different and lead to different distribution patterns of aquaporin 4 and -1.

No MeSH data available.


Related in: MedlinePlus

AQP4 and AQP1 expression (normalized to HPRT1) in SE and normal brain.A: AQP4 was upregulated in both SE subgroups (ΔCp -4.7 to -6.75) compared to normal brain (ΔCp -1.06/-1.09) (B). (ΔCp-values <-1 mean upregulation, >1 mean downregulation). B: Infratentorial SE show upregulated AQP1 expression (ΔCp -1.27 to -4.49) in contrast to supratentorial SE (ΔCp 1,83 to -1.44) and Normal Brain (ΔCp 1.81/2.48), which show a slight downregulation (A). Blue: patients 1–5 infratentorial SE, red: patients 6–10 supratentorial SE, green: Normal Brain as positive controls.
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pone.0131367.g005: AQP4 and AQP1 expression (normalized to HPRT1) in SE and normal brain.A: AQP4 was upregulated in both SE subgroups (ΔCp -4.7 to -6.75) compared to normal brain (ΔCp -1.06/-1.09) (B). (ΔCp-values <-1 mean upregulation, >1 mean downregulation). B: Infratentorial SE show upregulated AQP1 expression (ΔCp -1.27 to -4.49) in contrast to supratentorial SE (ΔCp 1,83 to -1.44) and Normal Brain (ΔCp 1.81/2.48), which show a slight downregulation (A). Blue: patients 1–5 infratentorial SE, red: patients 6–10 supratentorial SE, green: Normal Brain as positive controls.

Mentions: To investigate AQP4 expression on the RNA level, we performed PCR analysis with cDNAs of five infratentorial growing SEs (Fig 4A above lane 1–5) and five supratentorial SEs (Fig 4A above lane 6–10). Fig 4A above lane 11 is a negative control (H2O) and lane 12 a positive control (lung). The bottom lanes of Fig 4A show the respective HPRT1 expression. All SE samples seem to express AQP4 in more or less the same amount. Additionally, we performed Real-Time PCR analysis of AQP4 expression. The Cp-values were normalized to HPRT expression. The results (ΔCp-values) as shown in Fig 5A. The ΔCp-values for the infratentorial growing SEs vary only slightly between– 5.28 and– 6.53. Comparable results were achieved for the supratentorial SEs, which show Comparable results were achieved for the supratentorial SEs, which show ΔCp-values between– 4.7 and– 6.75. Summarized, these results show that the AQP4 expression is upregulated in SEs. In contrast, the Normal Brain Sample showed a ΔCp-values of– 1 (the two values are due to two different PCR-runs), indicating that there is no upregulation of AQP4 compared to HPRT1 expression in the healthy brain. T-Test analysis also revealed no significant difference between infra- and supratentorial samples concerning AQP4 expression (p = 0.8153). Compared to AQP4 expression of the Normal Brain both SE subsets (infra- and supratentorial) showed significant higher gene expression (p<0.0001 and p = 0.0008, respectively). The results showed AQP4 mRNA expression independent of the localization of the tumors.


Water Channels Aquaporin 4 and -1 Expression in Subependymoma Depends on the Localization of the Tumors.

Noell S, Fallier-Becker P, Mack AF, Hoffmeister M, Beschorner R, Ritz R - PLoS ONE (2015)

AQP4 and AQP1 expression (normalized to HPRT1) in SE and normal brain.A: AQP4 was upregulated in both SE subgroups (ΔCp -4.7 to -6.75) compared to normal brain (ΔCp -1.06/-1.09) (B). (ΔCp-values <-1 mean upregulation, >1 mean downregulation). B: Infratentorial SE show upregulated AQP1 expression (ΔCp -1.27 to -4.49) in contrast to supratentorial SE (ΔCp 1,83 to -1.44) and Normal Brain (ΔCp 1.81/2.48), which show a slight downregulation (A). Blue: patients 1–5 infratentorial SE, red: patients 6–10 supratentorial SE, green: Normal Brain as positive controls.
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pone.0131367.g005: AQP4 and AQP1 expression (normalized to HPRT1) in SE and normal brain.A: AQP4 was upregulated in both SE subgroups (ΔCp -4.7 to -6.75) compared to normal brain (ΔCp -1.06/-1.09) (B). (ΔCp-values <-1 mean upregulation, >1 mean downregulation). B: Infratentorial SE show upregulated AQP1 expression (ΔCp -1.27 to -4.49) in contrast to supratentorial SE (ΔCp 1,83 to -1.44) and Normal Brain (ΔCp 1.81/2.48), which show a slight downregulation (A). Blue: patients 1–5 infratentorial SE, red: patients 6–10 supratentorial SE, green: Normal Brain as positive controls.
Mentions: To investigate AQP4 expression on the RNA level, we performed PCR analysis with cDNAs of five infratentorial growing SEs (Fig 4A above lane 1–5) and five supratentorial SEs (Fig 4A above lane 6–10). Fig 4A above lane 11 is a negative control (H2O) and lane 12 a positive control (lung). The bottom lanes of Fig 4A show the respective HPRT1 expression. All SE samples seem to express AQP4 in more or less the same amount. Additionally, we performed Real-Time PCR analysis of AQP4 expression. The Cp-values were normalized to HPRT expression. The results (ΔCp-values) as shown in Fig 5A. The ΔCp-values for the infratentorial growing SEs vary only slightly between– 5.28 and– 6.53. Comparable results were achieved for the supratentorial SEs, which show Comparable results were achieved for the supratentorial SEs, which show ΔCp-values between– 4.7 and– 6.75. Summarized, these results show that the AQP4 expression is upregulated in SEs. In contrast, the Normal Brain Sample showed a ΔCp-values of– 1 (the two values are due to two different PCR-runs), indicating that there is no upregulation of AQP4 compared to HPRT1 expression in the healthy brain. T-Test analysis also revealed no significant difference between infra- and supratentorial samples concerning AQP4 expression (p = 0.8153). Compared to AQP4 expression of the Normal Brain both SE subsets (infra- and supratentorial) showed significant higher gene expression (p<0.0001 and p = 0.0008, respectively). The results showed AQP4 mRNA expression independent of the localization of the tumors.

Bottom Line: In contrast, aquaporin 1 RNA levels were found to be higher only in infratentorial samples compared to supratentorial and normal brain samples.On the cellular level, aquaporin 4 was redistributed on the surface of the tumor cells, and in freeze fracture replicas no orthogonal arrays of particles were found.This was similar to our previous findings in malignant glioblastomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, University of Tuebingen, Tuebingen, Germany.

ABSTRACT

Background: We analyzed aquaporin 4 and -1 expression in subependymomas, benign and slow growing brain tumors WHO grade I. Ten subependymoma cases were investigated, five of the fossa inferior and five of the fossa superior.

Methods and results: Using immunohistochemistry, we observed different aquaporin expression patterns depending on localization: aquaporin 4 and -1 were detected in infratentorial subependymomas in the entire tumor tissue. In contrast, supratentorial subependymomas revealed aquaporin 4 and -1 expression only in border areas of the tumor. PCR analyses however showed no difference in aquaporin 4 expression between all subependymomas independent of localization but at higher levels than in normal brain. In contrast, aquaporin 1 RNA levels were found to be higher only in infratentorial samples compared to supratentorial and normal brain samples. The reason for the different distribution pattern of aquaporin 4 in subependymomas still remains unclear. On the cellular level, aquaporin 4 was redistributed on the surface of the tumor cells, and in freeze fracture replicas no orthogonal arrays of particles were found. This was similar to our previous findings in malignant glioblastomas. From these studies, we know that extracellular matrix molecules within the tumor like agrin and its receptor alpha-dystroglycan are involved in forming orthogonal arrays of particles. In subependymomas neither agrin nor alpha-dystroglycan were detected around blood vessels.

Conclusions: Taken together, we show in this study that in the benign subependymomas aquaporins 1 and 4 are dramatically redistributed and upregulated. We speculate that extracellular environments of infra- and supratentorial subependymomas are different and lead to different distribution patterns of aquaporin 4 and -1.

No MeSH data available.


Related in: MedlinePlus