Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods ...Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods Seventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.Results Of the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P<0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P<0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P<0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P<0.05). There was a significant correlation between LVD and MVD (R=0.732, P<0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P<0.01).Conclusions In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.展开更多
Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapie...Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)展开更多
文摘Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods Seventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.Results Of the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P<0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P<0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P<0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P<0.05). There was a significant correlation between LVD and MVD (R=0.732, P<0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P<0.01).Conclusions In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81802296)Natural Science Foundation of Tianjin(Grant No.18JCQNJC82500)Tianjin Municipality Science and Technology Commission Projects(Grant No.12ZCDZSY15600).
文摘Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)
