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

主要的凝血和纤溶因子纤溶蛋白是由纤溶酶原（Plg）及其下游靶点之一基质金属蛋白酶（MMP）衍生而来的，它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淋巴瘤组织内mmp依赖性骨髓来源的CD11b+细胞的局部募集来降低淋巴瘤生长。遗传Plg缺陷和药物介导的纤溶酶阻断延迟淋巴瘤生长，减少MMP依赖的骨髓来源CD11b+细胞浸润到淋巴瘤组织和恶性生态位的形成。我们可以证明CD11b+细胞通过恶性生态位形成在淋巴瘤和其他恶性肿瘤的生长中发挥关键作用。总的来说，我们的数据证明了先前描述的纤维蛋白溶解系统在肿瘤生长中的作用，并提供了强有力的证据，表明特异性阻断纤溶蛋白是一种有希望的癌症治疗方法。

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.