Related Experiment Video
Updated: Oct 23, 2025
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
CD63-mediated cloaking of VEGF in small extracellular vesicles contributes to anti-VEGF therapy resistance
Shaolin Ma1, Lingegowda S Mangala2, Wen Hu3
1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
Abstract:
Despite wide use of anti-vascular endothelial growth factor (VEGF) therapy for many solid cancers, most individuals become resistant to this therapy, leading to disease progression. Therefore, new biomarkers and strategies for blocking adaptive resistance of cancer to anti-VEGF therapy are needed. As described here, we demonstrate that cancer-derived small extracellular vesicles package increasing quantities of VEGF and other factors in response to anti-VEGF therapy. The packaging process of VEGF into small extracellular vesicles (EVs) is mediated by the tetraspanin CD63. Furthermore, small EV-VEGF (eVEGF) is not accessible to anti-VEGF antibodies and can trigger intracrine VEGF signaling in endothelial cells. eVEGF promotes angiogenesis and enhances tumor growth despite bevacizumab treatment. These data demonstrate a mechanism where VEGF is partitioned into small EVs and promotes tumor angiogenesis and progression. These findings have clinical implications for biomarkers and therapeutic strategies for ovarian cancer.
Insights
Cancer cells release vascular endothelial growth factor (VEGF) in extracellular vesicles (EVs) that resist anti-VEGF therapy, promoting tumor growth. This discovery offers new therapeutic targets for overcoming treatment resistance in solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Anti-vascular endothelial growth factor (VEGF) therapy is widely used for solid cancers but often encounters resistance, leading to disease progression.
- New biomarkers and strategies are needed to overcome adaptive resistance to anti-VEGF therapy.
Purpose of the Study:
- To investigate the mechanism of adaptive resistance to anti-VEGF therapy in cancer.
- To identify novel biomarkers and therapeutic strategies for overcoming treatment resistance.
Main Methods:
- Analysis of cancer-derived small extracellular vesicles (EVs) packaging of VEGF in response to anti-VEGF therapy.
- Investigating the role of tetraspanin CD63 in VEGF packaging into EVs.
- Assessing the accessibility of EV-VEGF to antibodies and its effect on endothelial cells and tumor growth in vivo.
Main Results:
- Cancer cells package increasing amounts of VEGF into small EVs under anti-VEGF therapy.
- Tetraspanin CD63 mediates the packaging of VEGF into EVs.
- Small EV-VEGF (eVEGF) is resistant to anti-VEGF antibodies, triggers intracrine VEGF signaling, promotes angiogenesis, and enhances tumor growth despite bevacizumab treatment.
Conclusions:
- VEGF is partitioned into small EVs, promoting tumor angiogenesis and progression, representing a mechanism of resistance to anti-VEGF therapy.
- eVEGF has significant clinical implications for developing novel biomarkers and therapeutic strategies, particularly for ovarian cancer.
More Related Videos
09:24Three-dimensional Angiogenesis Assay System using Co-culture Spheroids Formed by Endothelial Colony Forming Cells and Mesenchymal Stem Cells
Published on: September 18, 2019
08:02In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:10Mechanism of Angiogenesis
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
01:27Tumor Immunotherapy