Inducible Nitric Oxide, Synthase in Renal Cell Carcinoma: Expression in Tumor Thrombi and Induction Under Hypoxic Conditions

Background: Nitric oxide (NO) has been suggested to have polar roles in carcinogenesis with both antitumor and tumor promoting activity, and the status of NO synthase (NOS) in renal cell carcinoma (RCC) has not yet been completely elucidated.

Materials And Methods: We investigated the expression and induction of inducible NOS (iNOS) in RCC specimens and cell lines, respectively.

Results: Although the expression of iNOS was not observed in primary lesions or in metastatic sites, it was found in 6 cases of 11 tumor thrombi. The cause-specific survival rate of patients with iNOS-positive tumor thrombi was lower than that of patients with iNOS-negative tumor thrombi, showing borderline significance. iNOS-mRNA and protein were expressed in A498 and A704 RCC cells under hypoxic conditions.

Conclusion: iNOS is suggested to be a significant molecule for RCC to acquire not only hypoxic adaptation but also the ability to invade into veins and form tumor thrombi.