The cells of a weakly tumorigenic and non-metastatic murine
fibrosarcoma (QR-32) are converted into highly malignant
tumors (acquiring metastatic potential) once they have grown in vivo after being co-implanted with
gelatin sponge which induces
inflammation. In the present study, we examined whether
nitric oxide (NO) is involved in the
inflammation-based
tumor progression by administrating a specific inhibitor to
inducible nitric oxide synthase,
aminoguanidine (AG). First, we co-implanted 1 x 10(5) QR-32 cells with
gelatin sponge (10 x 5 x 3 mm piece) into a subcutaneous space in C57BL6 mice. Administration of AG in
drinking water (1%) had started 2 days before the
tumor implantation and continued until the termination of the experiment. The incidence of
tumor formation and the
tumor growth did not differ between AG-treated group and -untreated group. On day 28, we excised the arising
tumors to establish culture cell lines for evaluation of their acquisition of metastatic phenotype in other normal mice.
Metastasis incidence and the number of metastatic colonies were significantly reduced in the tumor cell lines obtained from AG-treated mice compared to those from non-treated mice (p < 0.05). Immunohistochemical analysis demonstrated that
inducible nitric oxide synthase and
nitrotyrosine in the inflamed lesion were reduced in the AG-administered mice. However, intensity of 8-hydroxy-2-deoxyguanosine was not different between the groups. These results showed that
nitric oxide and its reactive
nitrogen oxide species cooperatively play a pivotal role in the progression of benign
tumor cells in inflamed lesions.