Li Xiuming, Song Dianbin, Liu Hui, Wang Zhiyong, Ma Guang, Yu Man, Zhang Yong, Zeng Yu
Department of Urology, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, P.R. China.
Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, School of Pharmacy, Minzu University of China, Beijing 100081, P.R. China.
Exp Ther Med. 2021 Jun;21(6):554. doi: 10.3892/etm.2021.9986. Epub 2021 Mar 26.
Renal cell carcinoma (RCC) is the most common form of kidney cancer. Vascular endothelial growth factor-C (VEGF-C) and its receptor, VEGFR-3, are involved in lymphangiogenesis. The aim of the present study was to investigate the expression levels of VEGF-C and VEGFR-3 in RCC, and their association with lymphatic vessel density (LVD) and lymph node metastasis. The mRNA expression levels of VEGF-C in 40 RCC tissues and 10 normal renal tissues were determined by reverse transcription-semiquantitative PCR. The differential expression of VEGF-C and VEGFR-3 was examined by immunohistochemistry. Using an anti-D2-40 antibody as a lymphatic marker, the morphology and structure of lymphatic vessels in tissues was examined, and the LVD was calculated. VEGF-C mRNA expression in RCC tissues was higher than that in normal renal tissues, and VEGF-C mRNA expression in the lymph node metastasis group was higher than that in the non-lymph node metastasis group. The positive expression rate of VEGF-C and VEGFR-3 in RCC tissues was significantly higher than that in normal renal tissues. VEGF-C expression in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group, and the positive expression of VEGF-C was associated with the clinical staging of RCC. In addition, there was a correlation between VEGF-C and VEGFR-3 expression in tumor cells. The LVD around the tumor was higher than that in the center of the tumor tissues and normal renal tissues, and it was closely associated with lymphatic invasion and lymph node metastasis. Overall, the current findings demonstrated that the VEGF-C/VEGFR-3 signaling pathway promoted lymphangiogenesis around the tumor and provided an approach for tumor lymphatic invasion and lymph node metastasis. Therefore, VEGFC and VEGFR-3 expression may serve an important role in the initiation and development of RCC.
肾细胞癌(RCC)是最常见的肾癌形式。血管内皮生长因子C(VEGF-C)及其受体VEGFR-3参与淋巴管生成。本研究的目的是调查VEGF-C和VEGFR-3在RCC中的表达水平,以及它们与淋巴管密度(LVD)和淋巴结转移的关系。通过逆转录-半定量PCR测定40例RCC组织和10例正常肾组织中VEGF-C的mRNA表达水平。采用免疫组织化学法检测VEGF-C和VEGFR-3的差异表达。使用抗D2-40抗体作为淋巴管标志物,检查组织中淋巴管的形态和结构,并计算LVD。RCC组织中VEGF-C mRNA表达高于正常肾组织,淋巴结转移组VEGF-C mRNA表达高于非淋巴结转移组。RCC组织中VEGF-C和VEGFR-3的阳性表达率显著高于正常肾组织。淋巴结转移组VEGF-C表达显著高于非淋巴结转移组,VEGF-C的阳性表达与RCC的临床分期相关。此外,肿瘤细胞中VEGF-C和VEGFR-3表达之间存在相关性。肿瘤周围的LVD高于肿瘤组织中心和正常肾组织,且与淋巴浸润和淋巴结转移密切相关。总体而言,目前的研究结果表明,VEGF-C/VEGFR-3信号通路促进肿瘤周围的淋巴管生成,并为肿瘤淋巴浸润和淋巴结转移提供了途径。因此,VEGFC和VEGFR-3表达可能在RCC的发生和发展中起重要作用。