Normal Wound Healing and Tumor Angiogenesis as a Game of Competitive Inhibition
Name
Kareva-2016-Normal Wound Healing and Tumor Ang.pdf
Size
2.29 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Kareva, Irina
Abou-Slaybi, Abdo
Dashevsky, Olga
Klement, Giannoula Lakka
Dodd, Oliver B.
Date Issued
December 2016
Journal
PLOS ONE
Publisher
Public Library of Science
Citation
Kareva, Irina et al. “Normal Wound Healing and Tumor Angiogenesis as a Game of Competitive Inhibition.” Ed. Jean-Léon Thomas. PLOS ONE 11.12 (2016): e0166655.
Version
Final published version
Abstract
Both normal wound healing and tumor angiogenesis are mitigated by the sequential, carefully orchestrated release of growth stimulators and inhibitors. These regulators are released from platelet clots formed at the sites of activated endothelium in a temporally and spatially controlled manner, and the order of their release depends on their affinity to glycosaminoglycans (GAG) such as heparan sulfate (HS) within the extracellular matrix, and platelet open canallicular system. The formation of vessel sprouts, triggered by angiogenesis regulating factors with lowest affinities for heparan sulfate (e.g. VEGF), is followed by vessel-stabilizing PDGF-B or bFGF with medium affinity for HS, and by inhibitors such as PF-4 and TSP-1 with the highest affinities for HS. The invasive wound-like edge of growing tumors has an overabundance of angiogenesis stimulators, and we propose that their abundance out-competes angiogenesis inhibitors, effectively preventing inhibition of angiogenesis and vessel maturation. We evaluate this hypothesis using an experimentally motivated agent-based model, and propose a general theoretical framework for understanding mechanistic similarities and differences between the processes of normal wound healing and pathological angiogenesis from the point of view of competitive inhibition.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0166655
