Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, Cracow, Poland.
Center of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow Branch, Warsaw, Poland.
Curr Pharm Biotechnol. 2019;20(12):1004-1010. doi: 10.2174/1389201020666190718164431.
Vascular endothelial growth factor (VEGF)-C, -D, and VEGF receptor-3 are proteins characterized as crucial for tumor lymphangiogenesis. It is accompanied by angiogenesis during wound healing, but also in the neoplastic process. The research studies have shown that the lymphatic system plays a key role in the progression of carcinogenesis.
The aim of this study was to evaluate changes in the expression of VEGF-C, VEGF-D and VEGFR-3 in different grades of endometrial cancer (G1-G3).
The study included 45 patients diagnosed with endometrial cancer (G1=17; G2=15; G3=13) and 15 patients without neoplastic changes. The expression of VEGF-C, VEGF-D, and VEGFR-3 was assessed using microarray technique and immunohistochemistry. Statistical analysis was performed using the one-way ANOVA and Tukey's post-hoc test.
Statistically significant changes in the expression at the transcriptome level were found only in the case of VEGF-C (G1 vs. C, fold change - FC = -1.15; G2 vs. C, FC = -2.33; G3 vs. C, FC = - 1.68). However, VEGF-D and VEGFR-3 were expressed at the protein level. Analysis of VEGF-D expression showed that the optical density of the reaction product in G1 reached 101.7, while the values in G2 and G3 were 142.7 and 184.4, respectively. For VEGF-R3, the optical density of the reaction product reached the following levels: 72 in control, 118.77 in G1, 145.8 in G2, and 170.9 in G3.
An increase in VEGF-D and VEGFR-3 levels may indicate that VEGF-D-dependent processes are intensified along with the dedifferentiation of tumor cells. The lack of VEGF-C expression in endometrial cancer samples may suggest that this tumor is characterized by a different mechanism of metastasis than EMT. Our study emphasizes that when analyzing the metastatic potential of cancer, the expression of more than one factor should be taken into account.
血管内皮生长因子 (VEGF)-C、-D 和 VEGF 受体-3 是被认为对肿瘤淋巴管生成至关重要的蛋白质。它伴随着伤口愈合时的血管生成，但也存在于肿瘤过程中。研究表明，淋巴系统在肿瘤发生的进展中起着关键作用。
本研究旨在评估不同分级子宫内膜癌 (G1-G3) 中 VEGF-C、VEGF-D 和 VEGFR-3 的表达变化。
本研究纳入了 45 例被诊断为子宫内膜癌的患者 (G1=17；G2=15；G3=13) 和 15 例无肿瘤变化的患者。使用微阵列技术和免疫组织化学评估 VEGF-C、VEGF-D 和 VEGFR-3 的表达。使用单向方差分析和 Tukey 事后检验进行统计学分析。
仅在 VEGF-C 的转录组水平上发现表达的统计学显著变化（G1 与 C 相比，倍数变化 (FC) = -1.15；G2 与 C 相比，FC = -2.33；G3 与 C 相比，FC = -1.68）。然而，VEGF-D 和 VEGFR-3 在蛋白质水平上表达。VEGF-D 表达分析表明，G1 中反应产物的光密度达到 101.7，而 G2 和 G3 中的值分别为 142.7 和 184.4。对于 VEGFR-3，反应产物的光密度达到以下水平：对照为 72，G1 为 118.77，G2 为 145.8，G3 为 170.9。
VEGF-D 和 VEGFR-3 水平的增加可能表明 VEGF-D 依赖性过程随着肿瘤细胞去分化而加剧。子宫内膜癌样本中 VEGF-C 表达的缺乏可能表明这种肿瘤的转移机制与 EMT 不同。我们的研究强调，在分析癌症的转移潜力时，应该考虑到一种以上因素的表达。
