The role of platelets in tumor growth, wound healing and other angiogenesis disease states The role of platelets in angiogenesis has been appreciated in the past both clinically and pre- clinically. We have recently published evidence that platelets actively sequester angiogenesis stimulators as well as inhibitors, and that there may be a higher organization of these opposing roles within platelet. This higher organization may facilitate the ability of platelets to modify angiogenesis in many angiogenesis-dependent disorders such as wound healing, atherosclerosis, tumor growth, macular degeneration and many others. Since the ability of platelets to enhance wound healing is restricted to intact platelets and does not extend to previously frozen platelets, the process most likely involves a reciprocal interaction between live, fully functional platelet and the wound microenvironment. Unlike other cells, platelets are destroyed by freezing. This proposal will a) characterize the molecular and cellular mechanisms by which platelets sequester and store angiogenesis regulators (Specific Aim 1); b) evaluate the mechanisms of release of these angiogenesis regulators from platelets (Specific Aim 2); c) test the potential therapeutic relevance of strategies designed to selectively release stimulators or inhibitors of angiogenesis from platelets in wound and tumor models (Specific Aim 3). The goal of these studies will be to provide a framework for development of novel targeted therapies for improvement of wound care, as well as for inhibition of tumor growth. It is expected that many agents that modify platelet function, secretion of proteins from platelets, and/or platelet adhesion will be applicable for management pathologic angiogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM093050-06
Application #
8825177
Study Section
Vascular Cell and Molecular Biology Study Section (VCMB)
Program Officer
Somers, Scott D
Project Start
2010-09-30
Project End
2014-08-31
Budget Start
2013-10-01
Budget End
2014-08-31
Support Year
Fiscal Year
2013
Total Cost
$163,833
Indirect Cost
$64,540
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
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Pilatova, Katerina; Greplova, Kristina; Demlova, Regina et al. (2013) Role of platelet chemokines, PF-4 and CTAP-III, in cancer biology. J Hematol Oncol 6:42
Etulain, J; Lapponi, M J; Patrucchi, S J et al. (2011) Hyperthermia inhibits platelet hemostatic functions and selectively regulates the release of alpha-granule proteins. J Thromb Haemost 9:1562-71