title: Tumor-derived vascular endothelial growth factor (VEGF)-a facilitates tumor metastasis through the VEGF-VEGFR1 signaling pathway.
abstract: Vascular endothelial growth factor (VEGF) and its receptors are involved in carcinogenesis, invasion and tumor angiogenesis, but the underlying mechanism by which VEGF promotes tumor metastasis is poorly understood. In this study, we show that in cancer patients high expression of VEGF is correlated with metastasis, and anti-VEGF treatment (bevacizumab) has clinical effects on tumor metastasis. Two human lung carcinoma cell lines (A549 and SPCA1 cells) with distinct VEGF expression were injected intravenously through the lateral tail vein of SCID mice and a murine model was developed. We investigated the association between the expression of VEGF and tumor metastasis by microvessel density, immunohistochemistry and whole mount staining. At sacrifice, in the high VEGF expression A549 cell line group, the induced tumor was distinctively larger in size and multiple metastatic lesions were found in lung tissues. Two specific neutralizing anti-mouse VEGFR1 and VEGFR2 antibodies were administered to the tumor-bearing mice; anti-VEGFR1, but not anti-VEGFR2 treatment produced inhibitive effects on VEGF-induced tumor metastasis. These findings demonstrate that the VEGF-VEGFR1 signaling pathway is crucial for tumor metastasis and the blockade of VEGF-VEGFR1-induced metastasis may provide a novel approach for the prevention and treatment of tumor metastasis.
authors.affiliation: Department of Immunology, Shandong Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, P.R. China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Liu
authors.forename: Jiying
authors.initials: J
authors.lastname: Xu
authors.forename: Mingming
authors.initials: M
authors.lastname: Wang
authors.forename: Qiangxiu
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuli
authors.initials: Y
authors.lastname: Bi
authors.forename: Mingyong
authors.initials: M
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1