Expression Profile of VEGF-C, VEGF-D, and VEGFR-3 in Different Grades of Endometrial Cancer

Abstract

Background: 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. Objective: 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). Methods: 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. Results: 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. Conclusion: : 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.

Curcumin in Combination With Omacetaxine Suppress Lymphoma Cell Growth, Migration, Invasion, and Angiogenesis via Inhibition of VEGF/Akt Signaling Pathway

“…Evidence has been shown that VEGF correlated with angiogenesis and tumor growth in NHLs and HLs ( 46 , 47 ). VEGF family members have already known to stimulate angiogenesis and enable tumor neovascularization ( 48 , 49 ). Hoeres et al.…”

“…Evidence has been shown that VEGF correlated with angiogenesis and tumor growth in NHLs and HLs (46,47). VEGF family members have already known to stimulate angiogenesis and enable tumor neovascularization (48,49). Hoeres et al found that lymphoma cell lines could produce VEGF, as well as release soluble VEGFR-1 simultaneously (50).…”

Dysregulated tumor-associated macrophages in carcinogenesis, progression and targeted therapy of gynecological and breast cancers

“…In breast cancer, TAM infiltration is closely associated with VEGF expression and microvascular density (MVD), which jointly affects the prognosis of patients [ 94 ]. In addition, previous studies have confirmed that VEGF-C, VEGF-D and their receptor VEGFR-3 were positively correlated with different stages of cervical lesions, allowing the development of lymphangion [ 95 , 96 ]. Interestingly, the expression of VEGF-C and VEGF-D increased significantly after the disease progressed to CIN3 stage [ 96 ].…”

“…Interestingly, the expression of VEGF-C and VEGF-D increased significantly after the disease progressed to CIN3 stage [ 96 ]. However, the opposite conclusion has been drawn in endometrial cancer [ 95 ]. One study reported that lower level of VEGF-C was detected in endometrial cancer samples [ 95 ].…”

HIV Associated Preeclampsia: A Multifactorial Appraisal

“…Specifically, VEGFs regulate cell proliferation, invasion and migration during angiogenesis [64]. Signal transduction of VEGF-A occurs via VEGFR-1 and VEGFR-2, whilst VEGF-B and PlGF activate VEGFR-1 [65], and VEGF-C and VEGF-D show an affinity for VEGFR-3 (Figure 2) [66].…”