TY - JOUR
T1 - Constitutive intracellular production of iNOS and NO in human melanoma
T2 - possible role in regulation of growth and resistance to apoptosis
AU - Grimm, Elizabeth A.
AU - Ellerhorst, Julie
AU - Tang, Chi Hui
AU - Ekmekcioglu, Suhendan
N1 - Funding Information:
The authors are grateful for the assistance of Engene T. Walch, Ph.D. in application of the DAF dye to our melanoma system. We also acknowledge the help of Omar Eton, M.D., and Antonio Buzaid, M.D, who directed the clinical trials in biochemotherapy on which the patients were enrolled. We are most grateful to Jeffrey E. Gershenwald and Victor Prieto for their support in tumor tissue acquisition and patient bioinformatics support. This work was supported by NIH SPORE in Melanoma, P50 CA093459 (EAG, JAE, SE) and by R21 CA111369 (JAE) and K22 CA097983 (JAE).
PY - 2008/9
Y1 - 2008/9
N2 - Human melanoma tumors cells are known to express the enzyme, inducible nitric oxide synthase (iNOS), which is responsible for cytokine induced nitric oxide (NO) production during immune responses. This constitutive expression of iNOS in many patients' tumor cells, as well as its strong association with poor patient survival, have led to the consideration of iNOS as a molecular marker of poor prognosis, as well as a possible target for therapy. The expression of iNOS in patient tumors was found to associate with nitrotyrosine, COX2, pSTAT3, and arginase. Using human melanoma patients' samples as well as cell lines, we have further evidence supporting intracellular NO production by detection of nitrotyrosine and also by use of DAF-2DA staining. Experiments were performed to scavenge the endogenous NO (with c-PTIO) resulting in melanoma cell growth inhibition; this was restored with SIN-1 (NO and O2-donor) providing data to support a functional role of this gas. Our goal is to understand the aberrant biology leading to this curious phenomenon, and to regulate it in favor of patient treatments.
AB - Human melanoma tumors cells are known to express the enzyme, inducible nitric oxide synthase (iNOS), which is responsible for cytokine induced nitric oxide (NO) production during immune responses. This constitutive expression of iNOS in many patients' tumor cells, as well as its strong association with poor patient survival, have led to the consideration of iNOS as a molecular marker of poor prognosis, as well as a possible target for therapy. The expression of iNOS in patient tumors was found to associate with nitrotyrosine, COX2, pSTAT3, and arginase. Using human melanoma patients' samples as well as cell lines, we have further evidence supporting intracellular NO production by detection of nitrotyrosine and also by use of DAF-2DA staining. Experiments were performed to scavenge the endogenous NO (with c-PTIO) resulting in melanoma cell growth inhibition; this was restored with SIN-1 (NO and O2-donor) providing data to support a functional role of this gas. Our goal is to understand the aberrant biology leading to this curious phenomenon, and to regulate it in favor of patient treatments.
KW - Biochemotherapy
KW - Melanoma
KW - Nitric oxide
KW - Nitrotyrosine
UR - http://www.scopus.com/inward/record.url?scp=47049084685&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47049084685&partnerID=8YFLogxK
U2 - 10.1016/j.niox.2008.04.009
DO - 10.1016/j.niox.2008.04.009
M3 - Article
C2 - 18472017
AN - SCOPUS:47049084685
SN - 1089-8603
VL - 19
SP - 133
EP - 137
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
IS - 2
ER -