Lymph node metastasis occurs in early-stage and late-stage ovarian cancers. Systematic lymphadenectomy is frequently conducted in an attempt to prevent disease progression. However, this method is associated with multiple complications. Therefore, it is necessary to develop a less invasive and more sensitive method for detecting lymphatic metastasis in ovarian cancer. The aim of the present study was to develop an appropriate fluorescent label for the analysis of lymphatic metastasis in vivo. To this end, epithelial ovarian cancer cells with high potential for lymph node metastasis were labeled using mCherry fluorescence. The cells were then imaged in vitro to determine the expression of mCherry, and in a mouse xenograft model in vivo. The data demonstrated the successful identification of metastatic retroperitoneal lymph nodes by co-localization with lymph nodes labeled by near-infrared fluorescence nanoparticles in vivo. These data provided important insights into the further development of methods for intra-operative identification of lymphatic metastasis and the mechanisms underlying lymphatic metastasis.

OBJECTIVE: To establish the retroperitoneal lymph node (RLN) metastasis model of cervical carcinoma in rabbits and evaluate the relationship of vascular endothelial growth factor-C (VEGF-C) expression and the lymph node status.
METHODS: Forty-eight rabbits were injected with VX2 cells or RPMI solution at muscular mucosae of the myometrium 0.5 cm away from the cervix. Animals were treated with or without cis-diamminedichloroplatinum(II) (cisplatin: DDP) and sacrificed on days 15, 21, and 27 post-VX2 or RPMI injections. Tumor mass and RLNs were examined histopathologically. Quantitative real-time PCR was used to examine the changes in VEGF-C mRNA expression. Levels of VEGF-C protein expression in tissues were determined using immunohistochemistry staining.
RESULTS: Development of VX2 cervical carcinoma and the RLNs metastasis was confirmed with pathological examination. Significantly increased tumor volume was observed on days 15, 21, and 27 postinjection (P<0.05). The enlargement of RLNs was found on day 21. Expression of VEGF-C was significantly upregulated in peripheral white blood cells, tumor mass, and RLNs in an association with cancer progression. DDP resulted in a suppression of VEGF-C expression, whereas the influences on tumor mass and lymphatic metastasis were insignificant.
CONCLUSIONS: Elevated VEGF-C expressions in peripheral white blood cells and RLNs are associated with tumor progression and lymphatic metastasis. DDP treatment inhibits VEGF-C expression and fails to protect against metastatic cervical cancer.