Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy.
<h4>Background</h4>Photodynamic therapy (PDT) uses the combination of photosensitizing drugs and harmless light to cause selective damage to tumor cells. PDT is therefore an option for focal therapy of localized disease or for otherwise unresectable tumors. In addition, there is increasi...
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oai:doaj.org-article:ac8ba1f4027a4e32aefeace7d07ee43e2021-11-18T06:50:51ZInduction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy.1932-620310.1371/journal.pone.0021834https://doaj.org/article/ac8ba1f4027a4e32aefeace7d07ee43e2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21738796/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Photodynamic therapy (PDT) uses the combination of photosensitizing drugs and harmless light to cause selective damage to tumor cells. PDT is therefore an option for focal therapy of localized disease or for otherwise unresectable tumors. In addition, there is increasing evidence that PDT can induce systemic anti-tumor immunity, supporting control of tumor cells, which were not eliminated by the primary treatment. However, the effect of non-lethal PDT on the behavior and malignant potential of tumor cells surviving PDT is molecularly not well defined.<h4>Methodology/principal findings</h4>Here we have evaluated changes in the transcriptome of human glioblastoma (U87, U373) and human (PC-3, DU145) and murine prostate cancer cells (TRAMP-C1, TRAMP-C2) after non-lethal PDT in vitro and in vivo using oligonucleotide microarray analyses. We found that the overall response was similar between the different cell lines and photosensitizers both in vitro and in vivo. The most prominently upregulated genes encoded proteins that belong to pathways activated by cellular stress or are involved in cell cycle arrest. This response was similar to the rescue response of tumor cells following high-dose PDT. In contrast, tumor cells dealing with non-lethal PDT were found to significantly upregulate a number of immune genes, which included the chemokine genes CXCL2, CXCL3 and IL8/CXCL8 as well as the genes for IL6 and its receptor IL6R, which can stimulate proinflammatory reactions, while IL6 and IL6R can also enhance tumor growth.<h4>Conclusions</h4>Our results indicate that PDT can support anti-tumor immune responses and is, therefore, a rational therapy even if tumor cells cannot be completely eliminated by primary phototoxic mechanisms alone. However, non-lethal PDT can also stimulate tumor growth-promoting autocrine loops, as seen by the upregulation of IL6 and its receptor. Thus the efficacy of PDT to treat tumors may be improved by controlling unwanted and potentially deleterious growth-stimulatory pathways.Robert KammererAlexander BuchnerPatrick PalluchThomas PongratzKonstantin OboukhovskijWolfgang BeyerAnn JohanssonHerbert SteppReinhold BaumgartnerWolfgang ZimmermannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e21834 (2011) |
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Medicine R Science Q Robert Kammerer Alexander Buchner Patrick Palluch Thomas Pongratz Konstantin Oboukhovskij Wolfgang Beyer Ann Johansson Herbert Stepp Reinhold Baumgartner Wolfgang Zimmermann Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. |
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<h4>Background</h4>Photodynamic therapy (PDT) uses the combination of photosensitizing drugs and harmless light to cause selective damage to tumor cells. PDT is therefore an option for focal therapy of localized disease or for otherwise unresectable tumors. In addition, there is increasing evidence that PDT can induce systemic anti-tumor immunity, supporting control of tumor cells, which were not eliminated by the primary treatment. However, the effect of non-lethal PDT on the behavior and malignant potential of tumor cells surviving PDT is molecularly not well defined.<h4>Methodology/principal findings</h4>Here we have evaluated changes in the transcriptome of human glioblastoma (U87, U373) and human (PC-3, DU145) and murine prostate cancer cells (TRAMP-C1, TRAMP-C2) after non-lethal PDT in vitro and in vivo using oligonucleotide microarray analyses. We found that the overall response was similar between the different cell lines and photosensitizers both in vitro and in vivo. The most prominently upregulated genes encoded proteins that belong to pathways activated by cellular stress or are involved in cell cycle arrest. This response was similar to the rescue response of tumor cells following high-dose PDT. In contrast, tumor cells dealing with non-lethal PDT were found to significantly upregulate a number of immune genes, which included the chemokine genes CXCL2, CXCL3 and IL8/CXCL8 as well as the genes for IL6 and its receptor IL6R, which can stimulate proinflammatory reactions, while IL6 and IL6R can also enhance tumor growth.<h4>Conclusions</h4>Our results indicate that PDT can support anti-tumor immune responses and is, therefore, a rational therapy even if tumor cells cannot be completely eliminated by primary phototoxic mechanisms alone. However, non-lethal PDT can also stimulate tumor growth-promoting autocrine loops, as seen by the upregulation of IL6 and its receptor. Thus the efficacy of PDT to treat tumors may be improved by controlling unwanted and potentially deleterious growth-stimulatory pathways. |
format |
article |
author |
Robert Kammerer Alexander Buchner Patrick Palluch Thomas Pongratz Konstantin Oboukhovskij Wolfgang Beyer Ann Johansson Herbert Stepp Reinhold Baumgartner Wolfgang Zimmermann |
author_facet |
Robert Kammerer Alexander Buchner Patrick Palluch Thomas Pongratz Konstantin Oboukhovskij Wolfgang Beyer Ann Johansson Herbert Stepp Reinhold Baumgartner Wolfgang Zimmermann |
author_sort |
Robert Kammerer |
title |
Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. |
title_short |
Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. |
title_full |
Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. |
title_fullStr |
Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. |
title_full_unstemmed |
Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. |
title_sort |
induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/ac8ba1f4027a4e32aefeace7d07ee43e |
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