Cali, B., Ceolin, S., Ceriani, F. orcid.org/0000-0002-5366-341X et al. (7 more authors) (2015) Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury. Oncotarget , 6 (12). pp. 10161-10174.
Abstract
Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding “bystander” cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely deined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca2+-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels signiicantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2015 Calì et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Keywords: | cancer; photodynamic therapy; nitric oxide; calcium signaling; connexins |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Jan 2017 16:36 |
Last Modified: | 09 Jan 2017 16:42 |
Published Version: | http://doi.org/10.18632/oncotarget.3553 |
Status: | Published |
Publisher: | Impact Journals |
Refereed: | Yes |
Identification Number: | 10.18632/oncotarget.3553 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108196 |