Establishment Of High Metastasis Model Of Human Ovarian Carcinoma Via VEGF-D Gene Transfection

Objective: Lymphogenous metastasis, one of the most common dissemination routes for ovarian carcinoma, indicates poor prognoses and corrolates to most cancer-related deaths. Vascular endothelial growth factor-d (VEGF-D) may contribute to tumor metastases via lymphangiogenesis. In this study we made an investigation on construction of lymphogenous high-metastasis model via VEGF-D gene transfection, to exploit tumor metastatic mechanisms, and hopefully to supply a bioplatform for preclinical screening and assessment of anti-metastasis agents or strategies.Methods: Human ovarian serous adenocarcinoma SK0V3 cells were transduced with VEGF-D recombinant plasmid DNA (SR); or with empty vector as controls (SV). Wild-type SK0V3 (SC), SV and SR cells were injected subcutaneously into the left footpads of nude mice, which had been demonstrated by us (in pre-experiments) to be an appropriate inoculation site for gaining higher lymphatic metastasis rates, and to conveniently observe and compare the tumorigeneses and metastases. Tumor growth were evaluated continuously. Evan's Blue in vivo lymphangiography was performed to delineate functional lymphatics. Levels of LYVE-1, VEGF-D MMP-2 and apoptosis in tumor tissues were examined by immunohistochemistry and Hoechst dyeing.Results: VEGF-D mRNA was exclusively expressed in SR group rather than SC and SV controls. Expression of VEGF-D protein can be tested in three groups, while the highest one was demonstrated in SR tumor mass. Compared with SV and SC controls, SR group showed much faster tumorigenesis and tumor growth, with denser functional lymphatic vessels, higher incidence of metastasis, higher-grade of MMP-2 staining and lower apoptotic index.Conclusions: This lymphogenous metastasis model demonstrates the important role of VEGF-D in stimulating lymphangiogenesis-induced lymphogenous metastasis and tumor growth in vivo. As a model giving higher and early metastasis, it can serve as a target point for molecular therapeutic modalities, and hopefully as a bioplatform for the screening and evaluation of antimetastasis agents or approaches.