Investigating the Functions of Thrombomodulin on Bone Marrow-Derived Mesenchymal Stem Cells

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Thrombomodulin (TM), a thrombin receptor on the endothelial cell surface, inhibits the pro-coagulant functions of thrombin and acts as a protein cofactor in thrombin-catalyzed activation of protein C. According to the widely expression patterns of TM on various cell types, our studies had evidenced that different TM domains participate in the regulations of cell-cell adhesion, tumor growth, angiogenesis, inflammation, and epithelial-mesenchymal transition. Recent reports proposed that bone marrow-derived mesenchymal stem cells (BM-MSCs) are specifically recruited to the stroma of developing tumors, which affects the tumor growth and metastasis. Moreover, it was found that TM is up-regulated on BM-MSCs upon its exposure to tumor cell conditioned medium, but the physiological function of TM in BM-MSCs remains unknown. Therefore, exploring the role of TM on BM-MSCs will help us to understand the biological role of TM on stem cells and may result in a new perspective on TM’s application for targeting and treating tumors. TM gene-targeting transgenic mouse isolated BM-MSCs will be used as a research model to implement four specific aims of this project, including (1) investigating the effect of TM deletion on BM-MSC’s differentiations, (2) determining the effect of TM deletion on BM-MSC’s biological activities, (3) exploring the molecular mechanism of TM expression and TM-mediated signaling pathways on BM-MSCs, and (4) examining the effect of TM deletion on BM-MSC-mediated tumor progression-related functions.

Project IDs

Project ID:PC10005-0027
External Project ID:NSC100-2320-B182-004
StatusFinished
Effective start/end date01/08/1131/07/12

Keywords

  • Thrombomodulin
  • TM gene-targeting transgenic mouse
  • bone marrow-derived mesenchymal stem cells

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