Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro.
Malignant gliomas are angiogenesis dependent and present a remarkable degree of resistance to radiotherapy. In the present work, we studied the effect of irradiation of C6 glioma cells on their proliferation and activation in vitro and on glioma cell-induced angiogenesis in vivo and in vitro. Irradiation of C6 glioma cells decreased cell proliferation in a dose-dependent manner. Interestingly, metalloproteinase-2 and -9 expression and secretion, as well as integrin alpha(v) expression, increased with elevated doses of X rays 48 hr after irradiation and was mostly evident at the higher doses used. When pre-irradiated C6 cells were implanted on nonirradiated chicken embryo chorioallantoic membranes (CAMs), there was a significant dose-dependent increase in tumor induced angiogenesis, compared to angiogenesis induced by nonirradiated cells. Similar results were obtained when C6 cells were irradiated 48 hr after their inoculation onto nonirradiated CAMs. In the same line, conditioned medium from irradiated C6 cells significantly increased endothelial cell proliferation and migration in vitro, in a manner dependent on the dose of X rays. These results explain at least in part the low effectiveness of radiation therapy of malignant gliomas and support the notion that inhibition of angiogenesis in parallel with radiotherapy may represent a new therapeutic approach.
Parthymou
Anastasia
A
Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, GR 26504, Greece.
Kardamakis
Dimitris
D
Pavlopoulos
Ionnis
I
Papadimitriou
Evangelia
E
D000482:Allantois / Q000098:blood supply / Q000528:radiation effects; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002823:Chorion / Q000098:blood supply / Q000528:radiation effects; D017931:DNA Primers; D004307:Dose-Response Relationship, Radiation; D005910:Glioma / Q000098:blood supply*; D049452:Green Fluorescent Proteins; D006801:Humans; D007700:Kinetics; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins