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Cancer-associated Fibroblasts-derived Exosomes with HOXD11 Overexpression Promote Ovarian Cancer Cell Angiogenesis
Chunfei Chen1, Fahui Wang1, Chunling Cheng1
1Department of Gynaecology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, P.R. China.
Reproductive Sciences (Thousand Oaks, Calif.)
|October 11, 2024
Summary
Cancer-associated fibroblasts (CAFs) release exosomes carrying homeobox protein hox-D11 (HOXD11), which promotes ovarian cancer (OC) angiogenesis by upregulating fibronectin 1 (FN1) and supporting tumor growth.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Cancer-associated fibroblasts (CAFs) are key players in the tumor microenvironment, promoting metastasis in ovarian cancer (OC).
- CAFs-derived exosomes (CAFs-Exo) are implicated in intercellular communication and tumor progression.
Purpose of the Study:
- To elucidate the mechanism by which CAFs-Exo promote angiogenesis in OC.
- To identify specific molecular cargos within CAFs-Exo responsible for this pro-angiogenic effect.
Main Methods:
- Differential gene expression analysis of OC cells treated with CAFs-Exo.
- Identification of transcription factors, including homeobox protein hox-D11 (HOXD11), as potential exosomal cargo.
- Functional assays assessing the impact of HOXD11 and fibronectin 1 (FN1) on OC cell behavior and angiogenesis.
- In vivo studies using mouse models to evaluate tumor growth and angiogenesis.
Main Results:
- HOXD11 was identified as a cargo of CAFs-Exo and enhanced OC cell proliferation, migration, and invasion.
- HOXD11 directly bound to the FN1 promoter, increasing its transcription.
- Knockdown of HOXD11 in CAFs-Exo significantly reduced VEGF and CD31 expression, impaired human umbilical vein endothelial cell (HUVEC) function, and inhibited angiogenesis and tumor growth in mice.
- FN1 overexpression rescued HUVEC activity in the context of HOXD11 knockdown.
Conclusions:
- CAFs-Exo contribute significantly to angiogenesis in OC.
- HOXD11 delivered by CAFs-Exo promotes OC angiogenesis, partly through the upregulation of FN1.
- Targeting the CAFs-Exo/HOXD11/FN1 axis presents a potential therapeutic strategy for ovarian cancer.
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