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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Glioblastoma | Research

Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients

Authors: Katerina Dvorakova, Veronika Skarkova, Barbora Vitovcova, Jiri Soukup, Hana Vosmikova, Zuzana Pleskacova, Adam Skarka, Michael Christian Bartos, Petr Krupa, Petra Kasparova, Jiri Petera, Emil Rudolf

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients.

Methods

The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too.

Results

Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers.

Conclusions

Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.
Appendix
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Metadata
Title
Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients
Authors
Katerina Dvorakova
Veronika Skarkova
Barbora Vitovcova
Jiri Soukup
Hana Vosmikova
Zuzana Pleskacova
Adam Skarka
Michael Christian Bartos
Petr Krupa
Petra Kasparova
Jiri Petera
Emil Rudolf
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12221-w

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