BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and beta1 integrin expression in ovarian cancer cells.
Benzoporphyrin derivative monoacid (BPD-MA) photosensitization was examined for its effects on cellular adhesion of a human ovarian cancer cell line, OVCAR 3, to extracellular matrix (ECM) components. Mild BPD-MA photosensitization (approximately 85% cell survival) of OVCAR 3 transiently decreased adhesion to collagen IV, fibronectin, laminin and vitronectin to a greater extent than could be attributed to cell death. The loss in adhesiveness was accompanied by a loss of beta1 integrin-containing focal adhesion plaques (FAPs), although beta1 subunits were still recognized by monoclonal antibody directed against human beta1 subunits. In vivo BPD-MA photosensitization decreased OVCAR 3 adhesiveness as well. Photosensitized adhesion was reduced in the presence of sodium azide and enhanced in deuterium oxide, suggesting mediation by singlet oxygen. Co-localization studies of BPD-MA and Rhodamine 123 showed that the photosensitizer was largely mitochondrial, but also exhibited extramitochondrial, intracellullar, diffuse cytosolic fluorescence. Taken together, these data show that intracellular damage mediated by BPD-PDT remote from the FAP site can affect cellular-ECM interactions and result in loss of FAP formation. This may have an impact on long-term effects of photodynamic therapy. The topic merits further investigation.
Runnels
J M
JM
Department of Dermatology, Massachusetts General Hospital, Boston 02114, USA.
Chen
N
N
Ortel
B
B
Kato
D
D
Hasan
T
T
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D017666:Deuterium Oxide / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000378:metabolism / Q000494:pharmacology*; D019810:Sodium Azide / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D; D019810:Sodium Azide; D002374:Catalase; D013482:Superoxide Dismutase; D017666:Deuterium Oxide