Hyper-Aggressiveness of Bystander Cells in an Anti-Tumor Photodynamic Therapy Model: Role of Nitric Oxide Produced by Targeted Cells. Crit Rev Oncog 2023;28(1):15-25
Date
10/12/2023Pubmed ID
37824384DOI
10.1615/CritRevOncog.2022040016Scopus ID
2-s2.0-85172468043 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
When selected tumor cells in a large in vitro population are exposed to ionizing radiation, they can send pro-survival signals to non-exposed counterparts (bystander cells). If there is no physical contact between irradiated and bystander cells, the latter respond to mediators from targeted cells that diffuse through the medium. One such mediator is known to be nitric oxide (NO). It was recently discovered that non-ionizing anti-tumor photodynamic therapy (PDT) can also elicit pro-survival/expansion bystander effects in a variety of human cancer cells. A novel silicone ring-based approach was used for distinguishing photodynamically-targeted cells from non-targeted bystanders. A key finding was that NO from upregulated iNOS in surviving targeted cells diffused to the bystanders and caused iNOS/NO upregulation there, which in turn stimulated cell proliferation and migration. The intensity of these responses depended on the extent of iNOS/NO induction in targeted cells of different cancer lines. Moreover, the responses could be replicated using NO from the chemical donor DETA/NO. This review will focus on these and related findings, their negative implications for clinical PDT, and how these might be averted by using pharmacologic inhibitors of iNOS activity or transcription.
Author List
Bazak J, Korytowski W, Girotti AWAuthor
Albert Girotti PhD, MS Emeritus Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisHumans
Neoplasms
Nitric Oxide
Photochemotherapy
Up-Regulation
