Depletion of chitinase-3-like protein 1 (CHI3L1) in glioma cells restraints tumor growth and affects neovasculature in intracranial murine gliomas Article Swipe
Bożena Kamińska
,
Salwador Cyranowski
,
Mitrajit Ghosh
,
Bartosz Wojtaś
,
Małgorzata Zawadzka
,
Szymon Baluszek
,
Julian Swatler
,
Kamil Wojnicki
,
Bartłomiej Gielniewski
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3208637/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3208637/v1
Chitinase-3-like protein 1 (CHI3L1) is a secreted, non-enzymatic glycoprotein that binds proteins and carbohydrates and interacts with cell-surface and extracellular-matrix proteins, proteoglycans, and polysaccharides. Multiple interacting partners of CHI3L1 make dissection of its functions challenging. While many studies reported an upregulation of CHI3L1 mRNA/protein in various tumors, its exact roles in tumorigenesis remain elusive. We performed a comprehensive analysis of CHI3L1 expression in multiple public datasets including TCGA and single-cell RNAseq datasets to determine the cellular source of CHI3L1 expression in gliomas. The highest CHI3L1 mRNA/protein levels were detected in glioblastoma (GBM), a high-grade diffusive brain tumor. CHI3L1 knockout in human U87-MG glioma cells grossly affected transcriptional profile and in vitro invasiveness of these cells and strongly reduced the growth of intracranial U87-MG tumors in athymic mice. Remarkably, CHI3L1 knockout in glioma cells resulted in normalization of tumor vasculature and diminished infiltration of glioma-associated myeloid cells. Mechanistically, CHI3L1 depleted cells had reduced MMP2 expression/activity, which was associated with reduced invasion; and downregulated SPP1 (osteopontin), a crucial factor driving myeloid cell accumulation in GBM. Altogether, we demonstrate that CHI3L1 is a key player in GBM progression, and its targeting represents a novel strategy to treat GBM patients.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3208637/v1
- https://www.researchsquare.com/article/rs-3208637/latest.pdf
- OA Status
- gold
- References
- 52
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385498148
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4385498148Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-3208637/v1Digital Object Identifier
- Title
-
Depletion of chitinase-3-like protein 1 (CHI3L1) in glioma cells restraints tumor growth and affects neovasculature in intracranial murine gliomasWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-08-02Full publication date if available
- Authors
-
Bożena Kamińska, Salwador Cyranowski, Mitrajit Ghosh, Bartosz Wojtaś, Małgorzata Zawadzka, Szymon Baluszek, Julian Swatler, Kamil Wojnicki, Bartłomiej GielniewskiList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-3208637/v1Publisher landing page
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https://www.researchsquare.com/article/rs-3208637/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-3208637/latest.pdfDirect OA link when available
- Concepts
-
Glioma, Chitinase, Cancer research, Brain tumor, Chemistry, Biology, Cell biology, Pathology, Medicine, Enzyme, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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52Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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