The role of plasmin in the pathogenesis of murine multiple myeloma
The role of plasmin in the pathogenesis of murine multiple myeloma
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DOI：
10.1016/j.bbrc.2017.05.062
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发表时间：
2017-06-24
影响因子：
3.1
通讯作者：
Heissig, Beate
中科院分区：
文献类型：
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作者：
Eiamboonsert, Salita;Salama, Yousef;Heissig, Beate
除了在凝块溶解中的作用外，纤溶因子纤溶酶还与肿瘤发生有关。虽然在多发性骨髓瘤患者中已经报道了凝血和纤溶异常，但使用体内模型尚未阐明纤溶因子在多发性骨髓瘤（MM）中的生物学作用。在这项研究中，我们建立了一个暴发型MM小鼠模型，骨髓和髓外移植后，静脉注射B53细胞。我们发现鼠B53 MM细胞中的纤溶因子表达模式与原代人MM细胞中报道的表达模式相似。使用纤溶酶抑制剂YO-2药理靶向纤溶酶并没有改变携带MM细胞的小鼠的疾病进展，尽管全身纤溶酶水平被抑制。我们的研究结果表明，尽管纤溶酶已被认为是使用大多数体外研究的MM临床患者样本的疾病进展的驱动因素，在此，我们证明了抑制纤溶酶生成或抑制纤溶酶不能改变体内MM进展。(C)2017爱思唯尔公司All rights reserved.
Aside from a role in clot dissolution, the fibrinolytic factor, plasmin is implicated in tumorigenesis. Although abnormalities of coagulation and fibrinolysis have been reported in multiple myeloma patients, the biological roles of fibrinolytic factors in multiple myeloma (MM) using in vivo models have not been elucidated. In this study, we established a murine model of fulminant MM with bone marrow and extramedullar engraftment after intravenous injection of B53 cells. We found that the fibrinolytic factor expression pattern in murine B53 MM cells is similar to the expression pattern reported in primary human MM cells. Pharmacological targeting of plasmin using the plasmin inhibitors YO-2 did not change disease progression in MM cell bearing mice although systemic plasmin levels was suppressed.Our findings suggest that although plasmin has been suggested to be a driver for disease progression using clinical patient samples in MM using mostly in vitro studies, here we demonstrate that suppression of plasmin generation or inhibition of plasmin cannot alter MM progression in vivo. (C) 2017 Elsevier Inc. All rights reserved.