To explore the effect of VEGF (vascular endothelial growth factor) on the vasculogenic mimicry (VM) formation of Choroidal Melanoma (CM) through PI3k signal pathway, to find novel targets for CM therapy.,This research investigated the molecular mechanism of VEGF promoting VM formation of CM.,First, we evaluated the expressions of VEGF in 20 CM specimens by immunohistochemical determination.,Then we detected expressions of VEGF, AKT, MT1-MMP, MMP2, and MMP9 of OCM-1 in hypoxia. siRNA was used to inhibit the expression of VEGF, to realize the control of the VM formation.,The VM formation was evaluated through wound healing assay, transwell assay, and apoptosis.,And then we testify the correlation of the VM and the factors in protein and mRNA level preliminarily.,VEGF protein was expressed in CM in all 20 cases of CM, especially along the VM.,In hypoxia, the expression of VEGF in OCM-1 increased significantly.,VEGF gene deletion reduced the proliferation, migration, and invasion of OCM-1.,VEGF gene deletion impaired the expression of invasive associated genes like VEGF, p-AKT, AKT, MT1-MMP, MMP2, and MMP9.,These results indicate that VEGF induce VM formation in CM by activating PI3K/AKT signaling pathway.,VEGF promoted VM formation by the PI3K signal transduction pathway, indicating a molecular mechanism which may be used to develop new therapeutic targets for the clinical treatment of CM.
Angiogenesis is important for the progression of cutaneous melanoma.,Here, we analyzed the prognostic impact of the angiogenic factor urokinase plasminogen activator resecptor (uPAR), vascular proliferation index (VPI) and tumor necrosis as a measure of hypoxia in a patient series of nodular melanomas (n = 255) and matched loco-regional metastases (n = 78).,Expression of uPAR was determined by immunohistochemistry and VPI was assessed by dual immunohistochemistry using Factor-VIII/Ki67 staining.,Necrosis was recorded based on HE-slides.,As novel findings, high uPAR expression and high VPI were associated with each other, and with increased tumor thickness, presence of tumor necrosis, tumor ulceration, increased mitotic count and reduced cancer specific survival in primary melanoma.,In matched cases, VPI was decreased in metastases, whereas the frequency of necrosis was increased.,Our findings demonstrate for the first time the impact on melanoma specific survival of uPAR expression and VPI in primary tumors, and of increased necrosis as an indicator of tumor hypoxia in loco-regional metastases.,These findings support the importance of tumor angiogenesis in melanoma aggressiveness, and suggest uPAR as an indicator of vascular proliferation and a potential biomarker in melanoma.