Release of regulators of angiogenesis following Hypocrellin-A and -B photodynamic therapy of human brain tumor cells.
Photodynamic therapy (PDT) is an innovative strategy for the treatment of solid neoplasms of the brain. Aside from inducing cell death in tumor cells, PDT induces endothelial cell death and promotes formation of blood clots; however, exact mechanisms that trigger these phenomena remain largely unknown. We now used Western blotting to analyze secretion of regulators of angiogenesis to the supernatants of one glioma, one macrophage, and one endothelial cell line following Hypocrellin-A and -B photodynamic therapy. We observed induction of proangiogenic VEGF (vascular endothelial growth factor) and of antiangiogenic sFlt-1, angiostatin, p43, allograft inflammatory factor-1, and connective tissue growth factor. Release of thrombospondin-1 was diminished in a glioma cell line supernatant. Endostatin release was induced in glioma cells and reduced in macrophages and endothelial cells. These data show that a wide range of antiangiogenic factors are secreted by brain tumor cells following Hypocrellin photochemotherapy. However, VEGF release is also induced thus suggesting both favorable and deleterious effects on tumor outgrowth.
Deininger
Martin H
MH
Institute of Brain Research, University of Tübingen, Calwer Strasse 3, D-72076 Tübingen, Germany. martin.deininger@uni-tuebingen.de
Weinschenk
Toni
T
Morgalla
Matthias H
MH
Meyermann
Richard
R
Schluesener
Hermann J
HJ
D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D013058:Mass Spectrometry; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019800:Phenol; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011809:Quinones / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D043925:Angiogenesis Inducing Agents; D017319:Photosensitizing Agents; D011809:Quinones; D019800:Phenol; D010569:Perylene; C048388:hypocrellin A; C064522:hypocrellin B