Abstract
Platelets have a crucial function in maintaining hemostasis. However, beyond their role in coagulation and thrombus formation, platelets have been implicated to affect various pathophysiological conditions such as infectious diseases, autoimmune disorders, and cancer. It is well-established that platelets aid local cancer growth by providing growth factors or contributing to cancer angiogenesis. In addition, they promote metastasis, among others by facilitation of tumor cell-extravasation and epithelial-to-mesenchymal-like transition as well as protecting metastasizing cancer cells from immunosurveillance. A variety of membrane-bound and soluble platelet-derived factors are involved in these processes, and many aspects of platelet biology in both health and disease are regulated by platelet-associated metalloproteinases and their inhibitors. Platelets synthesize (i) members of the matrix metalloproteinase (MMP) family and also inhibitors of MMPs such as members of the “tissue inhibitor of metalloproteinases” (TIMP) family as well as (ii) members of the “a disintegrin and metalloproteinase” (ADAM) family including ADAM10. Notably, platelet-associated metalloproteinase activity not only influences functions of platelets themselves: platelets can also induce expression and/or release of metalloproteinases e.g., in leukocytes or cancer cells, and ADAMs are emerging as important components by which platelets directly affect other cell types and function. This review outlines the function of metalloproteinases in platelet biology with a focus on ADAM10 and discusses the role of platelet-derived metalloproteinases in the interaction of platelets with components of the immune system and/or cancer cells.
Highlights
The main function of platelets in the healthy individual is maintenance of hemostasis, i.e., prevention of blood loss and protection of vascular integrity
We concluded that pADAM10 might be responsible for the enhanced shedding and may act via one of the suggested non-canonical shedding pathways: (i) cleavage exerted in trans or (ii) cleavage mediated by soluble (s)pADAM10, (iii) conferred by platelet-derived extracellular vesicles (EVs), or (iv) integration of pADAM10 in the substrate-bearing cell
The soluble form of ADAM10 may still exert proteolytic activity, it remains unclear under which instances or toward which targets [108]
Summary
The main function of platelets in the healthy individual is maintenance of hemostasis, i.e., prevention of blood loss and protection of vascular integrity. ADAMs IN PLATELETS by mechanistic studies describing substrates of pADAM10 and pADAM17 in platelets and confirming the expression of proteolytically active proteases. Collagen induced platelet activation itself was not dependent on ADAM9 [26] Along this line, studies of the ADAM9-downregulating micro-RNA miR-126 in CD34+ derived platelet-like structures and in the megakaryoblastic cell line MEG-01 confirmed ADAM9-mRNA expression, and did not identify a major role of pADAM9 in platelet activation [27, 28]. We here summarize studies deriving from different experimental strategies without applying restrictions e.g., a certain abundance in mass spec studies Using this approach, we identified a total of 35 putative and 3 confirmed substrates of pADAM10 on platelets (Table 1).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call