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.


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.


CONCLUSIONS
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.
Hara
Noboru
N
Division of Molecular Oncology, Department of Signal Transduction Research, Niigata University Graduate School of Medical and Dental Science, Asahimachi 1, Niigata 951, Japan.
Bilim
Vladimir
V
Kasahara
Takashi
T
Obara
Kenji
K
Saito
Kazuhide
K
Takahashi
Kota
K
Tomita
Yoshihiko
Y
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D013927:Thrombosis / Q000201:enzymology; D013997:Time Factors; D014407:Tumor Cells, Cultured
C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II