肿瘤转移是一项全球性的、迫切需要解决的重大科学问题。虽然肿瘤诊断和治疗水平已大幅提高，但大多数肿瘤患者仍时刻面临转移的威胁。如果能够通过药物改善血液微环境迫使循环肿瘤细胞(CTCs)难以存活，将有可能有效的预防肿瘤转移。基于对NO及其供体药物斯诺普利（CapNO）生物学特性和药理学活性的认识，我们推测NO、CapNO具有改善血液微环境的作用。我们前期研究发现NO及其供体CapNO能够抑制血小板活化、抑制CTCs在血管内皮细胞上的粘附，并通过同源小鼠肿瘤转移模型初步证明CapNO具有预防肿瘤转移的作用。本课题旨在阐明NO、CapNO通过改善血液微环境干预肿瘤血路转移的分子机制，包括研究NO、CapNO抑制内皮细胞黏附分子表达、抑制血小板-肿瘤细胞相互作用、增强免疫细胞活性从而改善血液微环境的分子机制。本研究将为通过改善血液微环境干预肿瘤转移的药物研发策略提供理论依据和技术支撑。

Metastasis is the principal cause of cancer-associated death and a major challenge in today's cancer management. Although many new diagnostic techniques and therapies against malignant tumors have been developed over the last years, the prognosis of most cancer survivors remains unfavorable. Therefore, it is very important to explore a new avenue, as namely “cancer metastasis chemoprevention”, to develop specific therapies to prevent cancer metastasis. Here we hypothesized that if we could creation of a hostile bloodstream microenvironment against circulating tumor cells (CTCs), we may efficiently prevent cancer metastatic cascade from initiation. Based on the Nitric oxide (NO) S-nitrosocaptopril (CapNO, a safe and effective NO donor drug) understanding of the biological characteristics and pharmacological activity, we presume that a series of the beneficial effects of NO and CapNO make the bloodstream microenvironment hostile to CTCs. Our previous study found that NO and CapNO inhibits platelet activation and hetero-adhesion of the CTCs to endothelial cells. Syngeneic mouse experimental metastatic models further demonstrated that CapNO have a remarkable inhibitory effect on cancer metastasis. In this study, we aim to clarify the molecular mechanism of interference cancer hematogenous metastases by NO and CapNO improve bloodstream microenvironment. Moreover, we will confirm the molecular mechanism of NO and CapNO inhibits endothelial cell adhesion molecules expression, platelet-CTCs interaction and enhance the immune cell activity. The studies will provide pre-clinical evidence and technical support for the cancer metastasis chemoprevention strategy by improve bloodstream microenvironment.