Direct correlation between nitric oxide synthase II inducibility and metastatic ability of UV-2237 murine fibrosarcoma cells carrying mutant p53

The relationship between nitric oxide synthase II (NOS II) inducibility and the metastatic ability of UV-2237 murine fibrosarcoma cells was determined . Highly metastatic cells survived to produce numerous lung metastases afte r i.v. injection in syngeneic C3H/HeN mice, whereas poorly metastatic cells did not. Highly metastatic clones exhibited higher levels of NOS II than d id poorly metastatic clones in response to interleukin la and IFN-gamma sti mulation. Furthermore, both poorly and highly metastatic clones contained a n identical p53 mutation. Overexpression of NOS II in a highly metastatic c lone by transfection with NOS II gene retarded tumor growth and completely suppressed metastasis, Our data indicate that a low to moderate level of NO S II expression directly correlates with metastatic ability of UV-2237 fibr osarcoma cells carrying mutant p53 and that a high level of nitric oxide pr oduction suppresses tumor growth and metastasis.