Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Normal wound healing and tumor angiogenesis as a game of competitive inhibition
Irina Kareva

Last modified: 2014-03-31


The process of normal wound healing and the process of tumor angiogenesis share a number of common characteristics, which has led to tumors being referred to as “wounds that do not heal”. Both processes are mitigated by growth factors, which are sequentially released from platelets at the wound site in an order that depends on their affinity to glycosaminoglycans within the extracellular matrix. Growth factors with lowest affinities (e.g. VEGF) commence formation of new blood vessels, followed by vessel-stabilizing cytokines with medium affinity (e.g. PDGF and bFGF), and followed by release of angiogenesis inhibitors with highest affinities (e.g. PF-4 and TSP-1). We propose that continual release of stimulators and stabilizers that often accompanies tumor growth prevents termination of the wound healing process through competitive inhibition. That is, cytokines with lower affinities out-compete inhibitors for binding sites on cells’ surface (as they will be released first from the platelet), effectively preventing vessel pruning. This hypothesis is evaluated using an experimentally validated agent-based model, and the results provide a mechanistic explanation for the differences between normal wound healing and pathological angiogenesis, as well as the angiogenesis occurring in dormant and actively growing tumors.


angiogenesis, wound healing, growth factors, competitive inhibition, agent-based modeling