The coagulation and the fibrinolytic system are essential drivers in the pathogenesis of leukemia and lymphoma

纤溶酶是一种主要的凝血和纤溶因子，它来源于纤溶酶原（Plg）及其下游靶点之一基质金属蛋白酶（MMP），与多种恶性肿瘤有关。在这里，我们提供的证据表明，阻断纤溶酶通过抑制MMP依赖性募集骨髓来源的CD11b+细胞局部淋巴瘤组织内减少淋巴瘤的生长。基因Plg缺陷和药物介导的纤溶酶阻断可延迟淋巴瘤的生长，减少MMP依赖的骨髓来源的CD11b+细胞浸润到淋巴瘤组织中和恶性小生境的形成。表明CD11b+细胞通过恶性小生境的形成在淋巴瘤及其他恶性肿瘤的生长中起关键作用。总的来说，我们的数据证明了纤溶系统在肿瘤生长中以前未描述的作用，并提供了强有力的证据，特异性阻断纤溶酶是一种有前途的癌症治疗方法。

The main coagulation and fibrinolytic factor plasmin, which is derived from its proform plasminogen (Plg) and one of its downstream targets, matrixmetalloproteinases (MMP), have been linked to various malignancies. Here, we provide the evidence that blockade of plasmin reduces lymphoma growth by inhibiting MMP-dependent recruitment of bone marrow derived CD11b+ cells locally within the lymphoma tissue. Genetic Plg deficiency and drug-mediated plasmin blockade delayed lymphoma growth and diminished MMP dependent marrow derived CD11b+ cell infiltration into lymphoma tissues and formation of malignant niche. We could show that CD11b+ cells play key a role in the growth of lymphoma and the other malignancies through malignant niche formation. Collectively, our data demonstrate a previously undescribed role of fibrinolytic system in tumor growth and provide strong evidence that specific blockade of plasmin a promising approach for the cancer treatments.