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Updated: May 30, 2026
Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
Published on: January 3, 2012
Clathrin-mediated entry and cellular localization of chlorotoxin in human glioma
Marzenna Wiranowska1, Lucrecia O Colina, Joseph O Johnson
1Department Pathology & Cell Biology, College of Medicine, University of South Florida, Tampa FL, USA. mwiranow@health.usf.edu.
Background:
Chlorotoxin (TM601), a scorpion venom- derived 36-AA peptide, is an experimental drug against recurrent glioma with tumor specificity but unknown route of intracellular distribution. The aim of this study was to evaluate the route of entry and cellular localization of TM601 in glioma cells.
Results:
We have found that in human gliomas, lung carcinoma and normal vascular endothelial cells, TM601 localizes near trans-Golgi while in normal human dermal fibroblasts (NHDF) and astrocytes it is dispersed in the cytoplasm. The uptake of TM601 by U373 glioma cells is rapid, concentration and time dependent, not affected by inhibitors such as filipin (caveolae-dependent endocytosis) and amiloride (non-selective macropinocytosis), but significantly affected by chlorpromazine (clathrin-dependent intracellular transport of coated pits) resulting in intracellular build-up of the drug and clathrin near the Golgi. In contrast, TM601 uptake by NHDF cells was significantly affected by amiloride indicating that macropinocytosis is the dominant uptake route of TM601 in these cells.
Conclusions:
In conclusion, we found a distinct cellular localization pattern and uptake of TM601 by glioma cells differing from that found in normal cells. Further insight into the cellular processing of TM601 should assist in the development of effective anti-glioma therapeutic modalities.
Insights
Chlorotoxin (TM601) shows distinct cellular uptake and localization in glioma cells compared to normal cells. Understanding TM601
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Chlorotoxin (TM601) is a scorpion venom-derived peptide investigated as an experimental treatment for recurrent glioma.
- TM601 exhibits tumor specificity, but its intracellular distribution in glioma cells remains unclear.
Purpose of the Study:
- To investigate the cellular entry pathways and localization of TM601 within glioma cells.
- To compare TM601's cellular processing in glioma cells versus normal cells.
Main Methods:
- Utilized U373 glioma cells and normal human dermal fibroblasts (NHDF).
- Assessed TM601 uptake and localization using various inhibitors (filipin, amiloride, chlorpromazine).
- Examined cellular localization near Golgi apparatus and cytoplasmic dispersion.
Main Results:
- TM601 localized near the trans-Golgi in glioma, lung carcinoma, and endothelial cells, but dispersed in the cytoplasm of NHDF and astrocytes.
- Glioma cell uptake was rapid, concentration- and time-dependent, and primarily clathrin-dependent.
- NHDF cells predominantly utilized macropinocytosis for TM601 uptake, as indicated by amiloride sensitivity.
Conclusions:
- TM601 exhibits differential cellular localization and uptake mechanisms in glioma cells compared to normal cells.
- Elucidating TM601's cellular processing is crucial for developing effective anti-glioma therapies.
