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Human malignant glioma therapy using anti-alpha(v)beta3 integrin agents.
S Chatterjee1, A Matsumura, J Schradermeier
1JCR Biopharmaceuticals, Inc., San Diego, CA 92121, USA. schat@jcrbio.com
Journal of Neuro-Oncology
|July 14, 2000
Summary
The cyclic peptide cRGDfV effectively induces apoptosis in human malignant glioma cells by targeting alpha(v)beta3 integrin. This peptide shows promise as a direct anti-tumor therapy for glioblastoma multiforme (GBM).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glioblastoma multiforme (GBM) is a fatal adult brain malignancy.
- Alpha(v)beta3 integrin is expressed on some human malignant glioma cells.
Purpose of the Study:
- To investigate the anti-tumor effects of the peptide cyclo-(Arg-Gly-Asp-D-Phe-Val) (cRGDfV) on human malignant glioma cells.
- To determine if cRGDfV induces apoptosis and affects cell survival in vitro and in vivo.
Main Methods:
- Immunofluorescence to detect alpha(v)beta3 integrin expression.
- In vitro treatment of glioma cells (U-87MG, U-373MG, U-251MG) with cRGDfV.
- Assessment of cell death using caspase inhibitors (DEVD-FMK, LEHD-FMK).
- In vivo studies using intracranial U-87MG tumors in scid mice.
Main Results:
- cRGDfV induced apoptosis and cell death in U-87MG and U-373MG cells expressing alpha(v)beta3 integrin, but not in U-251MG cells.
- Apoptosis was confirmed by blockage with caspase-3 and caspase-9 inhibitors.
- cRGDfV reduced spheroid formation in glioma cells.
- Treatment with cRGDfV significantly prolonged survival in mice with intracranial U-87MG tumors.
Conclusions:
- cRGDfV induces apoptosis in human glioma cells through binding to alpha(v)beta3 integrin.
- cRGDfV represents a potential non-toxic, direct anti-tumor therapy for alpha(v)beta3-expressing GBMs.