Eiamboonsert Salita, Salama Yousef, Watarai Hiroshi, Dhahri Douaa, Tsuda Yuko, Okada Yoshio, Hattori Koichi, Heissig Beate
Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Biochem Biophys Res Commun. 2017 Jun 24;488(2):387-392. doi: 10.1016/j.bbrc.2017.05.062. Epub 2017 May 10.
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.
除了在血栓溶解中发挥作用外，纤溶因子纤溶酶还与肿瘤发生有关。尽管在多发性骨髓瘤患者中已报道有凝血和纤溶异常，但利用体内模型研究纤溶因子在多发性骨髓瘤（MM）中的生物学作用尚未阐明。在本研究中，我们通过静脉注射B53细胞建立了一种具有骨髓和髓外植入的暴发性MM小鼠模型。我们发现，小鼠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对纤溶酶进行药理学靶向治疗，尽管全身纤溶酶水平受到抑制，但并未改变荷MM细胞小鼠的疾病进展。我们的研究结果表明，尽管在大多体外研究中，使用临床患者样本提示纤溶酶是MM疾病进展的驱动因素，但在此我们证明，抑制纤溶酶生成或抑制纤溶酶并不能在体内改变MM的进展。
