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Updated: May 10, 2026
Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics
Published on: June 23, 2022
Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas
Stine S Jensen1, Charlotte Aaberg-Jessen, Karina G Christensen
1Department of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Denmark.
Abstract:
Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded astrocytomas and compared with tumor grade and overall patient survival. Moreover, double immunofluorescence stainings were performed with LAMP-1 and the astrocytic marker GFAP and the putative stem cell marker CD133 on ten glioblastomas. Most tumors expressed the LAMP-1 protein in the cytoplasm of the tumor cells, while the blood vessels were positive in all tumors. The percentage of LAMP-1 positive tumor cells and staining intensities increased with tumor grade but variations in tumors of the same grade were also found. No association was found between LAMP-1 expression and patient overall survival in the individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem cells. Targeting of lysosomes may be a promising novel therapeutic strategy against this highly malignant neoplasm.
Insights
Lysosomes, marked by LAMP-1, are abundant in glioblastomas and their stem cells. Targeting these lysosomes offers a potential new therapy for brain tumors resistant to conventional treatments.
Area of Science:
- Oncology
- Cell Biology
- Neuroscience
Background:
- Targeting lysosomes presents a novel therapeutic strategy for overcoming apoptosis-resistant cancer cells.
- Glioblastoma, a highly malignant brain tumor, necessitates innovative treatment approaches.
- Lysosomes are crucial cellular organelles involved in degradation and recycling.
Purpose of the Study:
- To investigate lysosome presence in astrocytic brain tumors, including therapy-resistant tumor stem cells.
- To evaluate the expression of lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas.
- To correlate LAMP-1 expression with tumor grade, patient survival, and stem cell markers.
Main Methods:
- Immunohistochemistry was used to detect LAMP-1 expression in 112 astrocytomas.
- Double immunofluorescence staining was performed for LAMP-1, GFAP (astrocytic marker), and CD133 (stem cell marker) in ten glioblastomas.
- Expression levels were compared with tumor grade and patient overall survival.
Main Results:
- LAMP-1 protein was detected in the cytoplasm of tumor cells and in blood vessels across all tumors.
- Increased LAMP-1 expression correlated with higher tumor grade, though variations existed within grades.
- Co-expression of LAMP-1 with GFAP and CD133 indicated lysosomes are present in both tumor cells and putative stem cells.
Conclusions:
- Glioblastomas and their proposed tumor stem cells exhibit substantial lysosome content.
- Lysosome-targeting therapies show promise as a novel strategy against glioblastoma.
- Further research into lysosome-based treatments is warranted for this aggressive brain malignancy.
