ArticleCellular oncology (Dordrecht, Netherlands)2021
Cystatin F acts as a mediator of immune suppression in glioblastoma.
Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Cystatin F-a key player in central nervous system disease.Journal of neuroinflammation · 2025Review
- Targeting cystatin F activation enhances NK cell cytotoxicity in glioblastoma models.Frontiers in immunology · 2025Article
- Expression profiles and clinical significance of cystatin family genes in transitional cell carcinoma of the urinary bladder.Bladder (San Francisco, Calif.) · 2025Article
- Different glycosylation profiles of cystatin F alter the cytotoxic potential of natural killer cells.Cellular and molecular life sciences : CMLS · 2023Article
- Type 2 Cystatins and Their Roles in the Regulation of Human Immune Response and Cancer Progression.Cancers · 2023Review
- Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers.Clinical epigenetics · 2023Article
- Glioblastoma survival is associated with distinct proteomic alteration signatures post chemoirradiation in a large-scale proteomic panel.Frontiers in oncology · 2023Article
- Glioma-Associated Microglia Characterization in the Glioblastoma Microenvironment through a 'Seed-and Soil' Approach: A Systematic Review.Brain sciences · 2022Review
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- New inhibitors of cathepsin V impair tumor cell proliferation and elastin degradation and increase immune cell cytotoxicity.Computational and structural biotechnology journal · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
purposeGlioblastoma, the most aggressive type of brain cancer, is composed of heterogeneous populations of differentiated cells, cancer stem cells and immune cells. Cystatin F, an endogenous inhibitor of lysosomal cysteine peptidases, regulates the function of cytotoxic immune cells. The aim of this study was to determine which type of cells expresses cystatin F in glioblastoma and to determine the role of cystatin F during disease progression.
methodsRT-qPCR and immunohistochemistry were used to determine cystatin F mRNA and protein levels in glioblastoma tissue samples. The internalization of cystatin F was analyzed by Western blotting. Enzyme kinetics, real time invasion and calcein release cytotoxicity assays were used to assess the role of internalized cystatin F.
resultsWe found that cystatin F was not expressed in non-cancer brain tissues, but that its expression increased with glioma progression. In tumor tissues, extensive staining was observed in cancer stem-like cells and microglia/monocytes, which secrete cystatin F into their microenvironment. In trans activity of cystatin F was confirmed using an in vitro glioblastoma cell model. Internalized cystatin F affected cathepsin L activity in glioblastoma cells and decreased their invasiveness. In addition, we found that cystatin F decreased the susceptibility of glioblastoma cells to the cytotoxic activity of natural killer (NK) cells.
conclusionsOur data implicate cystatin F as a mediator of immune suppression in glioblastoma. Increased cystatin F mRNA and protein levels in immune, glioblastoma and glioblastoma stem-like cells or trans internalized cystatin F may have an impact on decreased susceptibility of glioblastoma cells to NK cytotoxicity.
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