Up-regulation of inducible nitric oxide synthase and production of nitric oxide by the swarm rat and human chondrosarcoma

Production of nitric oxide by solid tumors may have important ramifications regarding tumor growth and potential metastasis. This study demonstrated t hat the chondrosarcoma of the Swarm rat has upregulated mRNA for inducible nitric oxide synthase and produces nitric oxide. These results were confirm ed by (a) the presence of a 4.4-kb band of mRNA detected by Northern blot u sing a probe for inducible nitric oxide synthase, (b) a 133-kDa band of pro tein that was detected with either a polyclonal or monoclonal antibody to t he inducible nitric oxide synthase of the murine macrophage, and (c) the de tection of nitrites from the culture medium of freshly cultured, isolated c hondrosarcoma cells. This study showed that the expression of inducible nit ric oxide synthase and the production of nitric oxide by the tumor can be i ncreased by stimulation with endotoxin lipopolysaccharide and can be inhibi ted by inducible nitric oxide synthase inhibitors (L-N(g)-monomethyl argini ne and aminoguanidine). Immunostaining confirmed the presence of inducible nitric oxide synthase within the tumor cells and appeared to localize the e nzyme to the cytoplasm of the cells. A human chondrosarcoma was also shown to have an upregulated inducible nitric oxide synthase by both the detectio n of mRNA for inducible nitric oxide synthase and the presence of nitrites from the culture medium of the tumor in organ culture. Because the chondros arcoma of the Swarm rat is a well differentiated solid tumor that rarely me tastasizes, nitric oxide may be produced by the tumor to promote local grow th by effects on vascular supply.