VEGF-c expression in an in vivo model of orthotopic endometrial cancer and retroperitoneal lymph node metastasis
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RESEARCH
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VEGF-c expression in an in vivo model of orthotopic endometrial cancer and retroperitoneal lymph node metastasis Yong-Wen Huang1†, Li-Qun Xu1†, Rong-Zhen Luo2, Xin Huang1, Teng Hou1 and Yan-Na Zhang1*
Abstract Background: Retroperitoneal lymph node (RLN) metastasis is an important indicator of endometrial cancer (EC) prognosis. Because vascular endothelial growth factor c (VEGF-c) is known to influence lymphangiogenesis and thereby lymph node metastasis, this study assessed the relationship of VEGF-c mRNA expression with RLN metastasis in EC. Methods: The uterine muscularis mucosae of New Zealand white rabbits were inoculated with a VX2 tumor cell suspension after which they were sacrificed at 15, 18, 21, 24, 27 and 30 days. Control groups consisted of those receiving no treatment or an injection of saline. EC and metastatic RLN tissues along with peripheral blood samples were collected, and VEGF-c mRNA expression was evaluated using fluorescence real-time quantitative PCR. Results: The establishment of an in vivo model of EC with complete RLN metastasis was pathologically confirmed at day 21 post-injection with VX2 cells. As compared to the control groups, VEGF-c mRNA expression increased significantly over time in the tumor site, RLN, and peripheral white blood cells of EC rabbits. Significantly higher VEGF-c mRNA expression was observed in metastatic RLNs as compared to those without metastasis (P < 0.001). In addition, increased VEGF-c mRNA expression was observed in peripheral white blood cells of rabbits with RLN metastasis (P < 0.002). Conclusion: Injection of a VX2 cell suspension is a simple method of establishing an in vivo EC model. VEGF-c may play an important role in the development of EC and its metastasis to RLN and may be useful marker to predict RLN metastasis. Keywords: Vascular endothelial growth factor c, Endometrial cancer, Fluorescence real-time quantitative PCR, Disease animal model, Animal, Rabbit
Background Endometrial cancer (EC) is one of the most common malignancies of the female reproductive system [1]. Whereas patients with early-stage EC have a good prognosis, those with advanced EC usually develop retroperitoneal lymph node (RLN) metastasis with a 5-year survival rate, ranging from 30 to 40% [2-4]. Thus, it is crucial to develop new methods for predicting RLN metastasis in EC that can inform clinicians in selecting treatment modalities. * Correspondence: [email protected] † Equal contributors 1 Department of Gynecology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China Full list of author information is available at the end of the article
Analysis of a panel of angiogenic factors, including vascular endothelial growth factors (VEGF-A, -B, -C, D), matrix metalloproteinase-2 (MMP-2), and basic fibroblast growth factor (bFGF), in 16 gynecological cancer cell lines revealed that VEGF-c expression was significantly correlated with cell migration as well as MMP-2 levels [5]. VEGF-c i
