Retinoids induced t-PA synthesis by C6 glioma cells--role in tumoral haemorrhagic necrosis
| Autor: | G, Pernod, G, Amalfitano, B, Le Magueresse, F, Berger, B, Polack, L, Kolodié |
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| Rok vydání: | 1996 |
| Předmět: |
Brain Neoplasms
Fibrinolysis Antineoplastic Agents Glioma Neoplasm Proteins Rats Gene Expression Regulation Neoplastic Rats Sprague-Dawley Death Sudden Necrosis Tissue Plasminogen Activator Tumor Cells Cultured Animals Female RNA Messenger RNA Neoplasm Drug Screening Assays Antitumor Isotretinoin Neoplasm Transplantation Cerebral Hemorrhage |
| Zdroj: | Thrombosis and haemostasis. 75(2) |
| ISSN: | 0340-6245 |
| Popis: | Treatment of rat C6 glioma with high doses of 13 cis-retinoic acid (cRA) was responsible for death related to haemorrhagic necrosis localized to the tumor. Our aim was to explore this adverse effect of retinoid treatment. We show that cRA-treated C6 glioma at 25 mg/kg/day for 18 days exhibits in vivo an increase T-PA activity, which is responsible for a localized tumor fibrinolytic activity. Production of t-PA is supported by specific enhancement of gene expression, as was shown by the increase in t-PA mRNA (x 2.3). This production is a direct effect of cRA when treating the tumor, since tumor cells themselves do not produce enough t-PA and treatment of control rats does not increase the t-PA level. T-PA production by rat C6 glioma is in vivo related to the specific synthesis of t-PA by the C6 cell-line. The stimulation of C6 cell-line by cRA in vitro is dose-dependent and reached a maximum for 3 and 30 microM at the 72nd h. So cRA-treated C6 glioma cells produce t-PA which appears to be the major species associated with the fibrinolytic activity-induced intra-tumoral haemorrhage after exposure to retinoid treatment. |
| Databáze: | OpenAIRE |
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