title: Presence of intratumoral platelets is associated with tumor vessel structure and metastasis.
abstract: BACKGROUND
  Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics.
  
  
  METHODS
  Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-β) by ELISA.
  
  
  RESULTS
  Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-β. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation.
  
  
  CONCLUSIONS
  Our findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Meiping
authors.initials: M
authors.lastname: Ren
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.forename: Mao
authors.initials: M
authors.lastname: Luo
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Jiyi
authors.initials: J
authors.lastname: Xia
authors.forename: Guang
authors.initials: G
authors.lastname: Yu
authors.forename: Jinbo
authors.initials: J
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Ran
authors.affiliation: Drug Discovery Research Center, Luzhou Medical College, Luzhou, Sichuan, People's Republic of China. wuji@missouri.edu.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability; D004195:Disease Models, Animal; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D043925:Angiogenesis Inducing Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; D019859:Proto-Oncogene Proteins c-met; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9