Expression Of INOS And Its Relation To The Invasion And Metastasis In Colorectal Carcinoma

Invasion and metastasis of colorectal carcinoma is a complex process due to its multistage and many participated factors. This process includes the colorectal carcinoma cell dropping from original site, invasion and metastasis forming secondary neoplasm. Metastasis properties of tumor tissue are resulted from the changes in biological characters and the accumulation of pathological phenotype of subgroup clinic, gene phenotype, cell enzymology and cell adhesiveness so on. The direct contact between colorectal carcinoma cell and extracellular matrix (ECM), or the interactions among information molecules, make environment beneficial for the invasion and metastasis of tumor. Especially, the cell adhesiveness and invasion capacity, protease production for degrading ECM and cytokine excretion play the most important role on the invasion and metastasis of tumor. Gene expression of inducible nitric oxide synthase (iNOS) in colorectal carcinoma is generated from the development of cell enzymology, which is the usual event of molecular biology in human neoplasm. iNOS exerts an influence on inducing the nitric oxide (NO) generation. NO generation would affect the transmission between the intracellular second message and the nerve transmitter. Recently, considerable attentions have been paid to the effects of NO on proliferation, growth and death of tumor cell. NO could also promote tumor invasion by activating matrix metalloproteinases (MMPs), combine with endothelial cell surface receptor by vascularization promoter, enhance the expression of NOS by intracellular calmodulin and cyclohexanehexol phosphate, stimulate cell to produce NO and induce the cleavage and migrate of vascular endothelium and tumor angiogenesis.Proliferation and angiogenesis of malignant neoplasm are continuous process, and tumor cell could overexpress vascular endothelial growth factor (VEGF). NO could effectively promote the role of VEGF and affect expression of VEGF, which could regulate upward the NO expression. The effect of NO on tumor could be changed with NO concentration, tumor type and differentiation degree. Lower concentration of NO could promote the proliferation of tumor and angiogenesis, while higher NO could inhibit the cell growth by cytotoxic and DNA injury.NO could activate MMPs, but the mechanism is still not clear. It is possible that MMPs activation is resulted from the cysteine of MMP-9 triggered by S-Nitrosation by animal model of cerebral ischemia and reperfusion, which is followed by NOS accumulation and S-Nitrosation. NO could also induce the apoptosis of nerve cell by activating MMP-9 zymogen. Chemical reaction of NO is mainly determined by oxido-reduction. S-Nitroso derivative formed by the reaction between NO and cysteine mercaptan could adjust the biological reaction of some proteins. Furthermore, NO could increase urokinase plasminogen activator (uPA) during inducing the angiogenesis of capillary endothelial cell. uPA may converse plasminogen into plasmin to activate MMPs. This maybe is another pathway of destroying matrix of NO. Mechanism of tumor invasion and metastasis promoted by NO is up regulation of MMP-9 and down regulation of TIMP. These suggest that NO induced by iNOS in tumor tissue has important role on the MMP-9 and VEGF activation. However, the role and distribution of NO in colorectal carcinoma is so complex that only a little about iNOS distribution in colorectal carcinoma is known now. The present results are still not consistent.Neoplasm comes from the lost control of regulation on cell proliferation cycle and cell abnormal differentiation. The major reasons of tumor proliferation are uncontrolled check point of cell cycle and cycle protein expression. After 1980, it was reported that retinoic acid could induce differentiation and reversion. All-trans retinoic acid (ATRA) could adjust cell cycle of carcinoma. The mechanism may relate with the increased expression of kinase inhibitor depended by some cell cycle. It may inhibit carcinoma cell proliferation, decrease cell malignant phenotype and...