Cross-linking of signal transducer and activator of transcription 3--a molecular marker for the photodynamic reaction in cells and tumors.
OBJECTIVE
Photodynamic therapy (PDT) depends on the delivery of a photosensitizer to the target tissue that, under light exposure, produces singlet oxygen and other reactive oxygen species, which in turn cause the death of the treated cell. This study establishes a quantitative marker for the photoreaction that will predict the outcome of PDT.


METHODS
Cells in tissue culture, murine s.c. tumors, and endobronchial carcinomas in patients were treated with PDT, and the noncleavable cross-linking of the latent signal transducer and activator of transcription 3 (STAT3) was determined.


RESULTS
Murine and human cancer cell lines reacted to PDT by an immediate covalent cross-linking of STAT3 to homodimeric and other complexes. The magnitude of this effect was strictly a function of the PDT reaction that is determined by the photosensitizer concentration and light dose. The cross-link reaction of STAT3 was proportional to the subsequent cytotoxic outcome of PDT. An equivalent photoreaction as detected in vitro occurred in tumors treated in situ with PDT. The light dose-dependent STAT3 cross-linking indicated the relative effectiveness of PDT as a function of the distance of the tissue to the treating laser light source. Absence of cross-links correlated with treatment failure.


CONCLUSIONS
The data suggest that the relative amount of cross-linked STAT3 predicts the probability for beneficial outcome, whereas absence of cross-links predicts treatment failure. Determination of STAT3 cross-links after PDT might be clinically useful for early assessment of PDT response.
Henderson
Barbara W
BW
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Daroqui
Cecilia
C
Tracy
Erin
E
Vaughan
Lurine A
LA
Loewen
Gregory M
GM
Cooper
Michele T
MT
Baumann
Heinz
H
D000818:Animals; D001706:Biopsy; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008027:Light; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D016896:Treatment Outcome
D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D010100:Oxygen