Dexamethasone inhibits glioma-induced formation of capillary like structures in vitro and angiogenesis in vivo.
Dexamethasone is used frequently in brain tumor therapy of patients. In animal models it is known to inhibit the angiogenesis of solid tumors. We addressed the question, if this is also true in brain tumors. C6 malignant glioma and 9L gliosarcoma cells were implanted into rat-brains. Dexamethasone 3 mg/kg/d intraperitoneal increased the survival compared to saline treated controls. The tumors size and the vascular density were smaller in the dexamethasone groups in both models. In vitro dexamethasone inhibited the growth of the C6 cells but not of 9L cells. Thus the growth inhibition of brain tumors in vivo appeared to be mediated partly by direct growth inhibition of tumor cells in C6 cells but additionally by antiangiogenesis in both tumor models. Several in vitro models were used to address the mechanisms of antiangiogenesis. There was no effect of dexamethasone on the proliferation of central nervous endothelial cells and no effect on the formation of capillary like structures on matrigel. Dexamethasone inhibited, however, the formation of capillary like structures in a coculture model with glioma cells in vitro. Surprisingly, progesterone had the same effect in this model. The in vitro effect was mediated via glucocorticoid receptors since receptor antagonists could inhibit it. The primary target appeared to be the tumor cell because only this cell had the complete set of receptors. These data show, that antiangiogenic therapeutic effects are possible by influencing primarily the tumor cell. This way of targeting might be of value for future developments of new strategies.
Wolff
J E
JE
Department of Pediatric Oncology, University of Münster FRG.
Mölenkamp
G
G
Hotfilder
M
M
Laterra
J
J
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology; D002196:Capillaries / Q000187:drug effects; D002648:Child; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005909:Glioblastoma / Q000098:blood supply / Q000473:pathology; D005910:Glioma / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D018931:Antineoplastic Agents, Hormonal; D003907:Dexamethasone