Consecutive Observation of Dynamic Metastases of Human Ovarian Carcinoma to Grading Lymph Nodes in Mouse Model

Abstract Background：Lymphogenous metastasis, one of the most common dissemination routes for ovarian carcinoma, predicts a poor prognosis and relates to most cancer-related death. Now there were no effective therapy and control methods for ovarian carcinoma. Hence, it is necessary to build an animal model of lymph node metastasis in ovarian cancer to seek for the tools to find effective treatments. Our purpose of this study was to investigate the tumor cell dissemination of ovarian carcinoma to the gradient lymph nodes of nude mice and its possible mechanism.Methods: The mice models of VEGF-D over-expressed were built, and the tumor growth and sentinel lymph nodes were evaluated weekly, while the visible lymph nodes and tumor masses were excised for histological examination using HE examination. Then Evan’s Blue was conducted to observe the unveil lymphatic network. Subsequently, immunohistochemistry (IHC) was performed to check the protein expression of relative genes. Meanwhile, microvessel counting was performed within the tumor tissues and measured using computer assisted morphometric analysis.Results: The over-expression of VEGF-D promoted the tumor growth of ovarian carcinoma, facilitated the hyperplasia of tumor lymphatic and increased the intratumoral lymphatic vessel density. Besides, the up-regulation of VEGF-D induced the expression of MMP-2, which might be the underlying mechanism of the lymph metastasis in ovarian cancer.Conclusion: It was a step-by-step progression from the inoculation of cancer cells to the proliferation of the primary tumors, and then to the lymphatic metastases, in which VEGF-D and MMP-2 played vital roles.