De novo erythropoietin receptor (EPO-R) expression in human neoplastic glial cells decreases with grade of malignancy but is favourably associated with patient survival

Abstract

The erythropoietin receptor (EPO‐R) is mainly known as a regulator of erythropoiesis. However, recent studies revealed that the EPO‐R is not exclusively expressed in haematopoietic tissues but also in various cancer cell types and normal tissue such as the central nervous system (CNS). EPO‐R is up‐regulated under hypoxia and is able to counteract the deleterious effects of hypoxia on tumour growth, metastasis and treatment resistance. Therefore, the EPO–EPO‐R signalling pathway is considered as a possible target for tumour treatment. Here, we investigated brain tumour samples obtained from patients between 1993 and 2003 to study EPO‐R expression in vivo. Tissue samples included 194 gliomas of different WHO grades, additionally 25 infiltration zone samples and 31 relapses of WHO grade IV glioblastomas as well as 23 normal CNS tissue specimens to address the in vivo situation. Immunohistochemistry of the tissue microarray samples revealed significantly higher levels of EPO‐R expression in neoplastic glial cells compared with glial cells derived from normal brain. EPO‐R expression showed a highly significant decrease from low‐ to high‐grade gliomas. Age‐stratified Kaplan‐Meier analysis revealed longer survival for patients exhibiting high EPO‐R status in high‐grade gliomas. Our results show a grade‐dependent EPO‐R down‐regulation and might contribute to the understanding of high‐grade glioma resistance to radio‐ and chemotherapy as both were shown to be improved by a well functioning EPO–EPO‐R pathway in previous studies. Further studies are needed to investigate to what extent the decreased mortality in age‐stratified patient groups with high EPO‐R levels reflects a direct beneficial role of EPO‐R expression.

Autoren

M Mittelbronn
D Capper
B Bunz
K Dietz
B Goeppert
R Ajaaj
G Tabatabai
F Stubenvoll
H Schlaszus
AS Merseburger
R Becker
D Freudenstein
W Wick
M Weller
R Meyermann
P Simon

DOI

10.1111/j.1365-2990.2006.00820.x

eISSN

1365-2990

ISSN

0305-1846

Ausgabe der Veröffentlichung

3

Zeitschrift

Neuropathology and Applied Neurobiology

Sprache

en

Online publication date

2007

Paginierung

299 - 307

Datum der Veröffentlichung

2007

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1111/j.1365-2990.2006.00820.x

Datum der Datenerfassung

2023

Titel

<i>De novo</i> erythropoietin receptor (EPO‐R) expression in human neoplastic glial cells decreases with grade of malignancy but is favourably associated with patient survival

Ausgabe der Zeitschrift

33

Datenquelle: Crossref

Abstract

The erythropoietin receptor (EPO-R) is mainly known as a regulator of erythropoiesis. However, recent studies revealed that the EPO-R is not exclusively expressed in haematopoietic tissues but also in various cancer cell types and normal tissue such as the central nervous system (CNS). EPO-R is up-regulated under hypoxia and is able to counteract the deleterious effects of hypoxia on tumour growth, metastasis and treatment resistance. Therefore, the EPO-EPO-R signalling pathway is considered as a possible target for tumour treatment. Here, we investigated brain tumour samples obtained from patients between 1993 and 2003 to study EPO-R expression in vivo. Tissue samples included 194 gliomas of different WHO grades, additionally 25 infiltration zone samples and 31 relapses of WHO grade IV glioblastomas as well as 23 normal CNS tissue specimens to address the in vivo situation. Immunohistochemistry of the tissue microarray samples revealed significantly higher levels of EPO-R expression in neoplastic glial cells compared with glial cells derived from normal brain. EPO-R expression showed a highly significant decrease from low- to high-grade gliomas. Age-stratified Kaplan-Meier analysis revealed longer survival for patients exhibiting high EPO-R status in high-grade gliomas. Our results show a grade-dependent EPO-R down-regulation and might contribute to the understanding of high-grade glioma resistance to radio- and chemotherapy as both were shown to be improved by a well functioning EPO-EPO-R pathway in previous studies. Further studies are needed to investigate to what extent the decreased mortality in age-stratified patient groups with high EPO-R levels reflects a direct beneficial role of EPO-R expression.

Addresses

Institute of Brain Research (Neuropathology), University of Tuebingen, Tuebingen, Germany. michel-guy-andr.mittelbronn@med.uni-tuebingen.de

Autoren

M Mittelbronn
D Capper
B Bunz
K Dietz
B Goeppert
R Ajaaj
G Tabatabai
G Tabatabai
F Stubenvoll
H Schlaszus
AS Merseburger
R Becker
D Freudenstein
W Wick
M Weller
R Meyermann
P Simon

DOI

10.1111/j.1365-2990.2006.00820.x

eISSN

1365-2990

Externe Identifier

PubMed Identifier: 17493011

Open access

false

ISSN

0305-1846

Ausgabe der Veröffentlichung

3

Zeitschrift

Neuropathology and applied neurobiology

Schlüsselwörter

Humans
Glioma
Brain Neoplasms
Receptors, Erythropoietin
Tissue Array Analysis
Immunohistochemistry
Age Factors
Kaplan-Meier Estimate

Sprache

eng

Medium

Print

Paginierung

299 - 307

Datum der Veröffentlichung

2007

Status

Published

Datum der Datenerfassung

2007

Titel

De novo erythropoietin receptor (EPO-R) expression in human neoplastic glial cells decreases with grade of malignancy but is favourably associated with patient survival.

Sub types

Journal Article

Ausgabe der Zeitschrift

33

Datenquelle: Europe PubMed Central

Abstract

The erythropoietin receptor (EPO-R) is mainly known as a regulator of erythropoiesis. However, recent studies revealed that the EPO-R is not exclusively expressed in haematopoietic tissues but also in various cancer cell types and normal tissue such as the central nervous system (CNS). EPO-R is up-regulated under hypoxia and is able to counteract the deleterious effects of hypoxia on tumour growth, metastasis and treatment resistance. Therefore, the EPO-EPO-R signalling pathway is considered as a possible target for tumour treatment. Here, we investigated brain tumour samples obtained from patients between 1993 and 2003 to study EPO-R expression in vivo. Tissue samples included 194 gliomas of different WHO grades, additionally 25 infiltration zone samples and 31 relapses of WHO grade IV glioblastomas as well as 23 normal CNS tissue specimens to address the in vivo situation. Immunohistochemistry of the tissue microarray samples revealed significantly higher levels of EPO-R expression in neoplastic glial cells compared with glial cells derived from normal brain. EPO-R expression showed a highly significant decrease from low- to high-grade gliomas. Age-stratified Kaplan-Meier analysis revealed longer survival for patients exhibiting high EPO-R status in high-grade gliomas. Our results show a grade-dependent EPO-R down-regulation and might contribute to the understanding of high-grade glioma resistance to radio- and chemotherapy as both were shown to be improved by a well functioning EPO-EPO-R pathway in previous studies. Further studies are needed to investigate to what extent the decreased mortality in age-stratified patient groups with high EPO-R levels reflects a direct beneficial role of EPO-R expression.

Autoren

M Mittelbronn
D Capper
B Bunz
K Dietz
B Goeppert
R Ajaaj
G Tabatabai
F Stubenvoll
H Schlaszus
AS Merseburger
R Becker
D Freudenstein
W Wick
M Weller
R Meyermann
P Simon

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/17493011

DOI

10.1111/j.1365-2990.2006.00820.x

ISSN

0305-1846

Ausgabe der Veröffentlichung

3

Zeitschrift

Neuropathol Appl Neurobiol

Schlüsselwörter

Age Factors
Brain Neoplasms
Glioma
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Receptors, Erythropoietin
Tissue Array Analysis

Sprache

eng

Country

England

Paginierung

299 - 307

PII

NAN820

Datum der Veröffentlichung

2007

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2007

Titel

De novo erythropoietin receptor (EPO-R) expression in human neoplastic glial cells decreases with grade of malignancy but is favourably associated with patient survival.

Sub types

Journal Article

Ausgabe der Zeitschrift

33

Datenquelle: PubMed

De novo erythropoietin receptor (EPO-R) expression in human neoplastic glial cells decreases with grade of malignancy but is favourably associated with patient survival

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