Photodynamic therapy inhibits cell adhesion without altering integrin expression.
Adhesion is a primordial cell function that, among others, regulates inflammation, metastasis, and tissue repair. To understand how these events could be affected by photodynamic therapy (PDT), we studied the effects of PDT on human foreskin fibroblast (HFF) adhesion to bovine collagen type I, human vitronectin or fibronectin. PDT, using benzoporphyrin derivative monoacid ring A (verteporfin) as the photosensitizer, inhibited cell adhesion in a drug dose-dependent manner, with no significant difference among matrices. The drug dose that killed 90% of cells within 20 h post-treatment inhibited HFF adhesion by 55%-68%. However, 45 min following PDT, a time period corresponding to that of the adhesion assay, HFF membrane integrity remained unaltered. In addition, cell surface expression of integrins was not modified for at least 2h following PDT. Western blots of cell lysates, using the anti-phosphotyrosine 4G10 monoclonal antibody, revealed that PDT prevented the adhesion-induced phosphorylation of 110-130 kDa proteins. Immunoblots of cell lysates immunoprecipitated with antibodies to focal adhesion kinase suggested that its phosphorylation was suppressed by PDT. These results demonstrate that PDT inhibits cell adhesion and affects integrin signalling without modifying cell membrane integrity or integrin expression.
Margaron
P
P
QLT PhotoTherapeutics Inc., Vancouver, Canada. pmargaro@qlt-pdt.com
Sorrenti
R
R
Levy
J G
JG
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000528:radiation effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology / Q000528:radiation effects; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008027:Light; D010750:Phosphoproteins / Q000032:analysis; D010778:Photochemotherapy; D017319:Photosensitizing Agents; D011166:Porphyrins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000077362:Verteporfin
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D016023:Integrins; D010750:Phosphoproteins; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human