Increased in situ expression of nitric oxide synthase in human colorectal cancer

Abstract

There is growing evidence that nitric oxide (NO) has an important role in tumor growth. However, information on the expression of NO synthase (NOS) in colorectal cancers is scanty. We therefore investigated the distribution and expression of NOS in human colorectal cancers. The expression of three types of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS), was examined by immunohistochemistry in 25 cases of colorectal cancer. The expression of iNOS was also investigated at the mRNA level using the reverse transcriptase polymerase chain reaction (RT-PCR) in 6 cases. Correlations were made between iNOS expression and the histopathological findings. Immunoreactive iNOS was detected in the tumor cells in 22 cases (88%) with diffuse cytoplasmic reactions. Expression of iNOS-mRNA detected by RT-PCR in three tumor tissues was over five-fold that in normal mucosa. Intensified immunoreactivity of iNOS was associated with vascular invasion. iNOS expression did not correlate with pathological staging, tumor size, lymph node metastasis, p53 expression or tumor vessel density. Immunoreactive eNOS stained more strongly in the endothelial cells of microvessels within and around the tumor than in the areas remote from the tumor. There is enhanced expression of iNOS and eNOS in human colorectal cancers, which may correlate with tumor growth and vascular invasion.

Luteolin, a Bioflavonoid Inhibits Colorectal Cancer through Modulation of Multiple Signaling Pathways: A Review

“…To support further the role iNOS in colon tumor promotion, mice from an Apc Min/+ -iNOS-knockout genetic background showed decreased intestinal tumor formation (Ahn and Ohshima, 2001). In humans, iNOS expression is up-regulated in carcinomas compared with patient's normal-appearing colonic mucosa (Yagihashi et al, 2000). Luteolin has an anti-inflammatory role was already reported by modulating the inflammatory mediators (Choi, 2007).…”

Induction of HSF1 expression is associated with sporadic colorectal cancer

“…Recently, a large number of studies have revealed the association of iNOS expression with various cancers [35][36][37][38][39] . Yagihashi [40] studied 22 cases of colorectal cancer tissues by immunohistochemistry and RT-PCR and found increased iNOS expression was associated with colorectal cancer. Bing et al [37] found increased expression of iNOS and production of prostanoids in colorectal cancer paralleled to the increase in COX-2, confirming the importance of this emzyme in colon cancer.…”

Nitric oxide of human colorectal adenocarcinoma cell lines promotes tumour cell invasion

“…to upregulate their expression of NOS II and NO production (Witthoft et al, 1998). Enhanced expression of NOS II and NOS III has been recently discussed to correlate with tumour growth and vascular invasion in human colorectal cancer (Yagihashi et al, 2000;Lagares-Garcia et al, 2001). In our study the involvement of the NOS II isoform in Matrigel 1 invasion of the colorectal adenocarcinoma cell lines was evidenced by the inhibition of invasion by 1400 W, the most selective NOS II inhibitor reported to date.…”

“…Although the main source of NO probably are tumour-associated macrophages, there are some reports that the synthesis of NO is inducible by cytokines in some human carcinoma cell lines like DLD-1, HT-29, A-172 and NIH:OVCAR-3 (Thomsen and Miles, 1998). The biological significance of NO in malignant tumours is not clear, but a recent study suggest that a high expression of NOS II and NOS III is associated with aggressive behaviour of colorectal adenocarcinomas (Yagihashi et al, 2000). The aim of the present study was to investigate if NO is able to modulate tumour cell invasiveness of human colorectal adenocarcinoma cell lines , and whether NO can be induced by cytokines produced by stromal macrophages.…”