Nitric-oxide production by murine mammary adenocarcinoma cells promotes tumor-cell invasiveness.

摘要: The role of nitric oxide (NO) in tumor biology remains controversial and poorly understood. While a few reports indicate that the presence NO cells or their micro-environment is detrimental for tumor-cell survival, consequently metastatic ability, large body data suggests promotes progression. purpose this study was to identify source spontaneously metastasizing C3-L5 murine mammary-adenocarcinoma model, tumor-derived invasiveness, mechanisms underlying invasion-stimulating effects NO. established by immunocytochemical localization synthase (NOS) enzymes vitro transplanted tumors vivo. An transwell Matrigel invasion assay used test invasiveness absence blocking agents iNOS inducers (IFN-γ LPS). were examined measuring mRNA expression matrix metalloproteinases (MMP)-2 -9, tissue inhibitors (TIMP) 1, 2 3 various experimental conditions. Results showed expressed high level eNOS protein vitro, vivo, both primary tumors. also when cultured IFN-γ LPS. Constitutively produced promoted down-regulating TIMP 3. In addition, there up-regulation MMP-2, extra induced conclusion, altering balance between MMP-2 its TIMP-2 Thus, our earlier observations anti-tumor anti-metastatic vivo model can be explained, at least part, reduced invasiveness. Int. J. Cancer 81:889–896, 1999. © 1999 Wiley-Liss, Inc.