6533b82afe1ef96bd128c192

RESEARCH PRODUCT

Nitric Oxide Promotes Resistance to Tumor Suppression by CTLs

Ap BarreirosZhanhai SuSusanne StrandDennis StrandEdite Antunes FerreiraPeter R. GalleJürgen KuballMatthias TheobaldDaniela Gottfried

subject

ImmunologyCellNitric Oxide Synthase Type IIApoptosisBiologyEndoplasmic ReticulumNitric OxideCell LineMalignant transformationParacrine signallingImmune systemNeoplasmsmedicineHumansImmunology and AllergyCytotoxic T cellfas ReceptorAutocrine signallingMitochondriamedicine.anatomical_structureGene Expression RegulationApoptosisCell cultureMitochondrial MembranesImmunologyCancer researchSignal TransductionT-Lymphocytes Cytotoxic

description

Abstract Many human tumors express inducible NO synthetase (NOS2), but the roles of NO in tumor development are not fully elucidated. An important step during tumor development is the acquisition of apoptosis resistance. We investigated the dose-dependent effects of endogenously produced NO on apoptosis using ecdysone-inducible NOS2 cell lines. Our results show that short-term NOS2 expression enhances CD95-mediated apoptosis and T cell cytotoxicity dose dependently. Furthermore, we could show that during chronic exposure to NO, besides the primary cytotoxic NO effect, there is selection of cell clones resistant to NO that show cross-resistance to CD95-induced apoptosis and the killing by CTLs. We propose that NO production could initially act as an autocrine suicide or paracrine killing mechanism in cells undergoing malignant transformation. However, once failed, the outcome is fatal. NO promotes tumor formation by enhancing the selection of cells that can evade immune attack by acquiring apoptosis resistance.

yearjournalcountryeditionlanguage
2006-03-21The Journal of Immunology
https://doi.org/10.4049/jimmunol.176.7.3923