The role of plasmin in the pathogenesis of murine multiple myeloma
Salita Eiamboonsert1, Yousef Salama1, Hiroshi Watarai2
1Division 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.
Abstract:
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.
Insights
Plasmin, a fibrinolytic factor, is linked to cancer. This study found that inhibiting plasmin did not affect multiple myeloma progression in mice, challenging previous in vitro findings.
Area of Science:
- Hematology
- Oncology
- Biochemistry
Background:
- Plasmin, a fibrinolytic factor, plays a role in tumorigenesis.
- Coagulation and fibrinolysis abnormalities are reported in multiple myeloma (MM).
- The in vivo role of fibrinolytic factors in MM remains unclear.
Purpose of the Study:
- To investigate the biological roles of fibrinolytic factors in MM using in vivo models.
- To determine if targeting plasmin affects MM progression in a murine model.
Main Methods:
- Established a murine model of fulminant MM by intravenous injection of B53 cells.
- Analyzed fibrinolytic factor expression in murine MM cells.
- Administered plasmin inhibitors (YO-2) to MM-bearing mice.
Main Results:
- Murine B53 MM cells showed similar fibrinolytic factor expression to human MM cells.
- Pharmacological inhibition of plasmin did not alter MM disease progression in mice.
- Systemic plasmin levels were suppressed by plasmin inhibitors.
Conclusions:
- Plasmin inhibition or suppression does not alter MM progression in vivo.
- In vitro findings suggesting plasmin drives MM progression may not translate to in vivo settings.
- Further research is needed to understand the role of fibrinolysis in MM pathogenesis.
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