title: Procyanidins inhibit tumor angiogenesis by crosslinking extracellular matrix.
abstract: OBJECTIVE
  Procyanidins (PC) are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix (ECM) and preventing proteolysis by matrix metalloproteinases (MMPs).
  
  
  METHODS
  Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma.
  
  
  RESULTS
  PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC (0.75-100 µg/ml) did not inhibit vascular and tumor cells proliferation. PC injections (30 mg PC/kg bodyweight) in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs.
  
  
  CONCLUSIONS
  The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.
authors.affiliation: State Key Lab of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200068, China; ; Graduation School, Chinese Academy of Sciences, Beijing, China; ; Biomaterials and Tissue Engineering Research Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wan-Yin
authors.initials: WY
authors.lastname: Zhai
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Jia
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Yuan-Sen
authors.initials: YS
authors.lastname: Xu
keywords: Angiogenesis; Crosslinking; Extracellular matrix; Matrix metalloproteinases; Procyanidins