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Tumor suppressor role of the complement inhibitor CSMD1 and its role in TNF-induced neuroinflammation in gliomas

Tuysuz, Emre Can LU ; Mourati, Eleni LU ; Rosberg, Rebecca LU orcid ; Moskal, Aleksandra LU ; Gialeli, Chrysostomi LU ; Johansson, Elinn LU ; Governa, Valeria LU ; Belting, Mattias LU ; Pietras, Alexander LU and Blom, Anna M LU orcid (2024) In Journal of Experimental and Clinical Cancer Research 43. p.1-16
Abstract

BACKGROUND: The complement inhibitor CSMD1 acts as a tumor suppressor in various types of solid cancers. Despite its high level of expression in the brain, its function in gliomas, malignant brain tumors originating from glial cells, has not been investigated.

METHODS: Three cohorts of glioma patients comprising 1500 patients were analyzed in our study along with their clinical data. H4, U-118 and U-87 cell lines were used to investigate the tumor suppressor function of CSMD1 in gliomas. PDGFB-induced brain tumor model was utilized for the validation of in vitro data.

RESULTS: The downregulation of CSMD1 expression correlated with reduced overall and disease-free survival, elevated tumor grade, wild-type IDH genotype, and... (More)

BACKGROUND: The complement inhibitor CSMD1 acts as a tumor suppressor in various types of solid cancers. Despite its high level of expression in the brain, its function in gliomas, malignant brain tumors originating from glial cells, has not been investigated.

METHODS: Three cohorts of glioma patients comprising 1500 patients were analyzed in our study along with their clinical data. H4, U-118 and U-87 cell lines were used to investigate the tumor suppressor function of CSMD1 in gliomas. PDGFB-induced brain tumor model was utilized for the validation of in vitro data.

RESULTS: The downregulation of CSMD1 expression correlated with reduced overall and disease-free survival, elevated tumor grade, wild-type IDH genotype, and intact 1p/19q status. Moreover, enhanced activity was noted in the neuroinflammation pathway. Importantly, ectopic expression of CSMD1 in glioma cell lines led to decreased aggressiveness in vitro. Mechanically, CSMD1 obstructed the TNF-induced NF-kB and STAT3 signaling pathways, effectively suppressing the secretion of IL-6 and IL-8. There was also reduced survival in PDGFB-induced brain tumors in mice when Csmd1 was downregulated.

CONCLUSIONS: Our study has identified CSMD1 as a tumor suppressor in gliomas and elucidated its role in TNF-induced neuroinflammation, contributing to a deeper understanding of glioma pathogenesis.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental and Clinical Cancer Research
volume
43
article number
98
pages
1 - 16
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85189146386
  • pmid:38561856
ISSN
1756-9966
DOI
10.1186/s13046-024-03019-6
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
1f2d5d83-efe9-4056-a878-2b41c2b169b6
date added to LUP
2024-04-03 21:46:17
date last changed
2024-04-26 15:40:53
@article{1f2d5d83-efe9-4056-a878-2b41c2b169b6,
  abstract     = {{<p>BACKGROUND: The complement inhibitor CSMD1 acts as a tumor suppressor in various types of solid cancers. Despite its high level of expression in the brain, its function in gliomas, malignant brain tumors originating from glial cells, has not been investigated.</p><p>METHODS: Three cohorts of glioma patients comprising 1500 patients were analyzed in our study along with their clinical data. H4, U-118 and U-87 cell lines were used to investigate the tumor suppressor function of CSMD1 in gliomas. PDGFB-induced brain tumor model was utilized for the validation of in vitro data.</p><p>RESULTS: The downregulation of CSMD1 expression correlated with reduced overall and disease-free survival, elevated tumor grade, wild-type IDH genotype, and intact 1p/19q status. Moreover, enhanced activity was noted in the neuroinflammation pathway. Importantly, ectopic expression of CSMD1 in glioma cell lines led to decreased aggressiveness in vitro. Mechanically, CSMD1 obstructed the TNF-induced NF-kB and STAT3 signaling pathways, effectively suppressing the secretion of IL-6 and IL-8. There was also reduced survival in PDGFB-induced brain tumors in mice when Csmd1 was downregulated.</p><p>CONCLUSIONS: Our study has identified CSMD1 as a tumor suppressor in gliomas and elucidated its role in TNF-induced neuroinflammation, contributing to a deeper understanding of glioma pathogenesis.</p>}},
  author       = {{Tuysuz, Emre Can and Mourati, Eleni and Rosberg, Rebecca and Moskal, Aleksandra and Gialeli, Chrysostomi and Johansson, Elinn and Governa, Valeria and Belting, Mattias and Pietras, Alexander and Blom, Anna M}},
  issn         = {{1756-9966}},
  language     = {{eng}},
  month        = {{04}},
  pages        = {{1--16}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Experimental and Clinical Cancer Research}},
  title        = {{Tumor suppressor role of the complement inhibitor CSMD1 and its role in TNF-induced neuroinflammation in gliomas}},
  url          = {{http://dx.doi.org/10.1186/s13046-024-03019-6}},
  doi          = {{10.1186/s13046-024-03019-6}},
  volume       = {{43}},
  year         = {{2024}},
}