Tumors stimulate platelet delivery of angiogenic factors in vivo: an unexpected benefit

Am J Pathol. 2008 Dec;173(6):1609-16. doi: 10.2353/ajpath.2008.080474. Epub 2008 Nov 6.


The interaction between platelets and the tumor microenvironment results in the modulation of angiogenesis, although the mechanisms governing this regulation remain unclear. This study explores the differences in the communication between wounded tissues and healthy, tumor-conditioned, and frozen platelets. Platelet-rich plasma obtained from healthy (PRP) or tumor-bearing (TPRP) mice was applied to dorsal, full-thickness wounds on diabetic mice. Wound healing was evaluated using macroscopic criteria and a staging system based on angiogenesis and stromal cell proliferation. Proteomic analysis was used to compare the levels of angiogenic proteins contained in the platelet preparations. TPRP-treated wounds reached 90% wound closure 5.6 to 9.5 days earlier than PRP-treated and nontreated wounds, respectively. TPRP induced a fourfold increase in stromal cell proliferation compared with nontreated wounds, and a 2.5-fold increase compared with PRP-treated wounds. TPRP induced the highest stimulation of angiogenesis with a fourfold increase compared with nontreated controls. On day 21, wounds treated with TPRP showed a typical architecture with thick collagen bundles. Although the levels of angiogenesis regulators detected via SELDI-ToF were similar between the PRP and TPRP treatment regimens, the enhanced healing capacity of TPRP suggests improved platelet delivery as indicated by frozen TPRP preparations that had lost most of their pro-angiogenic drive. In conclusion, these results show that intact tumor-conditioned platelets display an improved ability to deliver angiogenesis regulators to wounded tissues.

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Animals
  • Blood Platelets / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Neoplasms / metabolism*
  • Neovascularization, Physiologic / physiology*
  • Plasma / chemistry
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Random Allocation
  • Skin / anatomy & histology
  • Skin / injuries
  • Skin / pathology
  • Wound Healing / physiology


  • Angiogenesis Inducing Agents
  • Platelet Endothelial Cell Adhesion Molecule-1