Abstract |
The transforming growth factor (TGF)-β signaling pathway has been recognized as a major factor in promoting the aggressive behavior of glioblastoma, isocitrate dehydrogenase-wildtype. However, there is little knowledge about the expression of TGF-β receptors in glioblastoma. Here, we studied the expression patterns of TGF-β receptor II (TGFβRII), type I receptors activin receptor-like kinase (ALK)-5, and ALK-1, as well as of the transcriptional regulators inhibitor of differentiation (Id) 2, Id3, and Id4 in human glioblastoma. The expression of TGFβRII, ALK-5, and ALK-1 varied greatly, with TGFβRII and ALK-5 being the most abundant and ALK-1 being the least expressed receptor. None of the 3 receptors was preferentially expressed by tumor vasculature as opposed to the tumor bulk, indicating tumor bulk-governed mechanisms of TGF-β signaling with regard to glioblastoma-associated angiogenesis. A positive correlation was found between ALK-1 and Id2, suggesting that Id2, broadly expressed in the tumor cells, is a downstream target of this receptor-dependent pathway. Furthermore, there was a trend for high expression of ALK-5 or Id2 to be associated with inferior overall survival. Hence, we propose that ALK-5 may be used for patient stratification in future anti-TGF-β treatment trials and that Id2 might be a potential target for anti-TGF-β interventions.
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Authors | Claudio Togni, Emanuel Rom, Isabel Burghardt, Patrick Roth, Elisabeth J Rushing, Michael Weller, Dorothee Gramatzki |
Journal | Journal of neuropathology and experimental neurology
(J Neuropathol Exp Neurol)
Vol. 81
Issue 3
Pg. 225-235
(02 24 2022)
ISSN: 1554-6578 [Electronic] England |
PMID | 35190826
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 American Association of Neuropathologists, Inc. All rights reserved. |
Chemical References |
- Receptors, Transforming Growth Factor beta
- Transforming Growth Factor beta
- Transforming Growth Factors
- Isocitrate Dehydrogenase
- Receptor Protein-Tyrosine Kinases
- Protein Serine-Threonine Kinases
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Topics |
- Glioblastoma
(genetics)
- Humans
- Isocitrate Dehydrogenase
(genetics)
- Prognosis
- Protein Serine-Threonine Kinases
- Receptor Protein-Tyrosine Kinases
(metabolism)
- Receptors, Transforming Growth Factor beta
(genetics, metabolism)
- Signal Transduction
- Transforming Growth Factor beta
(metabolism)
- Transforming Growth Factors
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