Interleukin-6 trans signalling enhances photodynamic therapy by modulating cell cycling

Photodynamic therapy (PDT) of solid tumours causes tissue damage that elicits local and systemic inflammation with major involvement of interleukin-6 (IL-6). We have previously reported that PDT-treated cells lose responsiveness to IL-6 cytokines. Therefore, it is unclear whether PDT surviving tumou...

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Bibliographic Details
Published in:British journal of cancer Vol. 97; no. 11; pp. 1513 - 1522
Main Authors: Wei, L-H, Baumann, H, Tracy, E, Wang, Y, Hutson, A, Rose-John, S, Henderson, B W
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 03.12.2007
Nature Publishing Group
Subjects:
Animals
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Cancer Research
cdc25 Phosphatases - metabolism
Cell cycle
Cell Cycle - drug effects
Cell Cycle - physiology
Cell growth
Cell Line, Tumor
Cell Proliferation - drug effects
Chlorophyll - analogs & derivatives
Chlorophyll - pharmacology
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Culture Media, Conditioned - pharmacology
Cyclin E - metabolism
Cyclin-Dependent Kinase 2 - metabolism
Cyclin-Dependent Kinase Inhibitor p27 - metabolism
Cytokines
Dose-Response Relationship, Drug
Drug Resistance
Epidemiology
HeLa Cells
Humans
Inflammation
Interleukin-6 - metabolism
Interleukin-6 - pharmacology
Interleukin-6 - physiology
Macrophages - drug effects
Macrophages - metabolism
Medical research
Medical sciences
Mice
Mice, Inbred BALB C
Molecular Medicine
Oncology
Penicillin
Photochemotherapy
Photodynamic therapy
Receptors, Interleukin-6 - metabolism
Signal Transduction - physiology
STAT3 Transcription Factor - metabolism
Thoracic surgery
Translational Therapeutics
Tumors
United States > US
soluble interleukin-6 receptor
cell cycle
photodynamic therapy
interleukin-6
Interleukin 6
Signal transduction
Cancerology
Photodynamic therapy
Cell therapy
Treatment
Interleukin 6 receptor
Cytokine
Cell cycle
Soluble form
ISSN:0007-0920, 1532-1827
Online Access:Get full text
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Summary:Photodynamic therapy (PDT) of solid tumours causes tissue damage that elicits local and systemic inflammation with major involvement of interleukin-6 (IL-6). We have previously reported that PDT-treated cells lose responsiveness to IL-6 cytokines. Therefore, it is unclear whether PDT surviving tumour cells are subject to regulation by IL-6 and whether this regulation could contribute to tumour control by PDT. We demonstrate in epithelial tumour cells that while the action of IL-6 cytokines through their membrane receptors is attenuated, regulation by IL-6 via trans-signalling is established. Soluble interleukin-6 receptor- α (IL-6R α ) (sIL-6R α ) and IL-6 were released by leucocytes in the presence of conditioned medium from PDT-treated tumour cells. Cells that had lost their membrane receptor IL-6R α due to PDT responded to treatment with the IL-6R–IL-6 complex (Hyper-IL-6) with activation of signal transducers and activator of transcription (STAT3) and ERK. Photodynamic therapy-treated cells, which were maintained during post-PDT recovery in presence of IL-6 or Hyper-IL-6, showed an enhanced suppression of proliferation. Cytokine-dependent inhibition of proliferation correlated with a decrease in cyclin E, CDK2 and Cdc25A, and enhancement of p27kip1 and hypophosphorylated Rb. The IL-6 trans-signalling-mediated attenuation of cell proliferation was also effective in vivo detectable by an improved Colon26 tumour cure by PDT combined with Hyper-IL-6 treatment. Prevention of IL-6 trans-signalling using soluble gp130 reduced curability. The data suggest that the post-PDT tumour milieu contains the necessary components to establish effective IL-6 trans-signalling, thus providing a means for more effective tumour control.
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ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6604073