RELATIONSHIPS OF NO WITH NOSIP, MMP-2/9 AND TIMP-2 IN HUMAN COLORECTAL CANCER

Abstract

Background/aim: Gelatinases (matrix metalloproteinases/MMP-2 and -9) have a key role during progression of colorectal cancers (CRCs). The imbalance between tissue inhibitor metalloproteinases (TIMP-2) and MMPs results in pathological outcomes. Previous studies indicate that gelatinases and TIMP-2 are stimulated by nitric oxide (NO). NO has been reported to exert both tumoricidal and tumor promoting effects at different stages of many cancer types. Therefore, control of NO production may be important for progression of cancer. Nitric oxide synthase interacting protein (NOSIP), an inhibitor of eNOS and nNOS enzymes, leads to a tissue preservation process. Thus, we assume that NOSIP may play an important role in progression of CRC. Tumorous tissue, normal tissue and plasma were collected from 17 CRC patients, and normal plasma was collected from 17 healthy individuals. Tissue samples were used for q-RT-PCR assay and plasmas for nitrite/nitrate quantification and ELISA analysis. The levels of NO, MMP-2 and MMP-9 increased in the plasma of CRC patients, whereas level of NOSIP protein decreased and amount of TIMP-2 did not change. Gelatinase gene expressions were found to be higher and the levels of NOSIP gene expression lower, but TIMP-2 gene expressions did not differ in CRC samples. We suggested that NO may interfence activities of MMP-2 and -9 in CRC patients as a result of a reduction in NOSIP level. NOSIP protein and NOSIP gene expression levels were determined for the first time in human cancerous tissues.