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Updated: Aug 4, 2025

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Tregs are involved in VEGFA/ VASH1-related angiogenesis pathway in ovarian cancer
Sijing Qiao1, Yue Hou1, Qing Rong1
1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, People's Republic of China; College of Medicine, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, People's Republic of China; Key Laboratory of Gynecology Oncology of Shandong Province, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, People's Republic of China; Shandong Engineering Laboratory for Urogynecology; Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, People's Republic of China.
Abstract:
Vasohibin1 (VASH1) is a kind of vasopressor, produced by negative feedback from vascular endothelial growth factor A (VEGFA). Anti-angiogenic therapy targeting VEGFA is currently the first-line treatment for advanced ovarian cancer (OC), but there are still many adverse effects. Regulatory T cells (Tregs) are the main lymphocytes mediating immune escape function in the tumor microenvironment (TME) and have been reported to influence the function of VEGFA. However, whether Tregs are associated with VASH1 and angiogenesis in TME in OC is unclear. We aimed to explore the relationship between angiogenesis and immunosuppression in the TME of OC. We validated the relationship between VEGFA, VASH1, and angiogenesis in ovarian cancer and their prognostic implications. The infiltration level of Tregs and its marker forkhead box protein 3 (FOXP3) were explored in relation to angiogenesis-related molecules. The results showed that VEGFA and VASH1 were associated with clinicopathological stage, microvessel density and poor prognosis of ovarian cancer. Both VEGFA and VASH1 expression were associated with angiogenic pathways and there was a positive correlation between VEGFA and VASH1 expression. Tregs correlated with angiogenesis-related molecules and indicated that high FOXP3 expression is harmful to the prognosis. Gene set enrichment analysis (GSEA) predicted that angiogenesis, IL6/JAK/STAT3 signaling, PI3K/AKT/mTOR signaling, TGF-β signaling, and TNF-α signaling via NF-κB may be common pathways for VEGFA, VASH1, and Tregs to be involved in the development of OC. These findings suggest that Tregs may be involved in the regulation of tumor angiogenesis through VEGFA and VASH1, providing new ideas for synergistic anti-angiogenic therapy and immunotherapy in OC.
Insights
Regulatory T cells (Tregs) may influence ovarian cancer (OC) angiogenesis via vasohibin1 (VASH1) and vascular endothelial growth factor A (VEGFA). This suggests new therapeutic strategies combining anti-angiogenic and immunotherapy for OC treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Anti-angiogenic therapy targeting vascular endothelial growth factor A (VEGFA) is a standard treatment for advanced ovarian cancer (OC), but faces challenges like adverse effects and resistance.
- Regulatory T cells (Tregs) are key players in tumor immune escape and can influence VEGFA function within the tumor microenvironment (TME).
- The specific roles of vasohibin1 (VASH1) and Tregs in OC angiogenesis and their interplay within the TME remain largely unexplored.
Purpose of the Study:
- To investigate the relationship between angiogenesis and immunosuppression in the TME of OC.
- To validate the association of VEGFA and VASH1 with angiogenesis and their prognostic significance in OC.
- To explore the correlation between Treg infiltration, specifically forkhead box protein 3 (FOXP3) expression, and angiogenesis-related molecules in OC.
Main Methods:
- Analysis of VEGFA and VASH1 expression in relation to clinicopathological features, microvessel density, and patient prognosis in OC.
- Assessment of Treg infiltration (FOXP3+) and its correlation with angiogenesis markers.
- Gene set enrichment analysis (GSEA) to identify common signaling pathways involving VEGFA, VASH1, and Tregs in OC development.
Main Results:
- VEGFA and VASH1 expression levels were significantly associated with advanced clinicopathological stage, increased microvessel density, and poorer prognosis in OC patients.
- A positive correlation was observed between VEGFA and VASH1 expression, both linked to pro-angiogenic pathways.
- High FOXP3 expression in Tregs correlated with angiogenesis-related molecules and was associated with unfavorable patient outcomes.
Conclusions:
- VEGFA and VASH1 are important prognostic factors in OC and are implicated in tumor angiogenesis.
- Tregs may contribute to OC progression by regulating tumor angiogenesis through VEGFA and VASH1.
- These findings highlight potential synergistic therapeutic strategies for OC, combining anti-angiogenic treatments with immunotherapy targeting Tregs.
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