Abstract
BackgroundPlatelets 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.MethodsUsing 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.ResultsPlatelet 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.ConclusionsOur findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis.
Highlights
Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells
Platelet depletion showed no change in tumor growth and reduced lung metastasis Previous studies demonstrated that circulating platelets play a shielding role in cancer cell dissemination and hemorrhagic metastasis [1,2,3]
Until the experimental endpoint, plateletdepleted mice showed no change in tumor growth (2777 ± 300 mm3 Vs. 2956 ± 180 mm3, p > 0.05) (Figure 1A, B) compared to control mice, while B16/F10 tumor-bearing platelet-depleted mice exhibited a significant reduction in lung metastasis compared to control mice (Figure 1C)
Summary
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, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. It is unclear that platelet depletion affects tumor vessel structure and dynamics. Experimental evidence suggests that the depletion of platelets results in anti-tumor dissemination in thrombocytopenic mice [4,5,6,7]. It has been proposed that platelets may play a direct role in the mobilization of primary tumor cells to vessels for metastasis. The current study was designed to test the hypothesis that platelets influence metastasis by mediating tumor vessel structure and dynamics
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