Back to Search
Start Over
Sublethal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma
- Source :
- Cancer research. 61(6)
- Publication Year :
- 2001
-
Abstract
- Human malignant gliomas are highly lethal neoplasms. Involved-field radiotherapy is the most important therapeutic measure. Most relapses originate from the close vicinity of the irradiated target field. Here, we report that sublethal doses of irradiation enhance the migration and invasiveness of human malignant glioma cells. This hitherto unknown biological effect of irradiation is p53 independent, involves enhanced alphavbeta3 integrin expression, an altered profile of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9) expression and activity, altered membrane type 1 MMP and tissue inhibitor of metalloproteinases-2 expression, and an altered BCL-2/BAX rheostat favoring resistance to apoptosis. BCL-2 gene transfer and irradiation cooperate to enhance migration and invasiveness in a synergistic manner. Sublethal irradiation of rat 9L glioma cells results in the formation of a greater number of tumor satellites in the rat brain in vivo concomitant with enhanced MMP-2 and reduced tissue inhibitor of metalloproteinases-2 expression. Collectively, these data suggest that the current concepts of involved-field radiotherapy for malignant glioma need to be reconsidered and that the pharmacological inhibition of migration and invasion during radiotherapy may represent a new therapeutic approach to improve the therapeutic efficacy of radiotherapy for malignant glioma.
- Subjects :
- Male
Brain Neoplasms
3T3 Cells
Glioma
Radiation Tolerance
Rats, Inbred F344
Rats
Mice
Matrix Metalloproteinase 9
Proto-Oncogene Proteins c-bcl-2
Cell Movement
Spheroids, Cellular
Tumor Cells, Cultured
Animals
Humans
Matrix Metalloproteinase 2
Neoplasm Invasiveness
Receptors, Vitronectin
Glioblastoma
Subjects
Details
- ISSN :
- 00085472
- Volume :
- 61
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.pmid..........4805535c4afd541e11ef7a69e0634868