ArticleCell reports2021
CD63-mediated cloaking of VEGF in small extracellular vesicles contributes to anti-VEGF therapy resistance.
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Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Extracellular Vesicle-Mediated Regulation of H3C14 Contributes to Gemcitabine Resistance in Bladder Cancer.Journal of extracellular vesicles · 2025Article
- HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3-containing extracellular vesicles.The Journal of clinical investigation · 2025Article
- Comparative Examination of Feline Coronavirus and Canine Coronavirus Effects on Extracellular Vesicles Acquired from A-72 Canine Fibrosarcoma Cell Line.Veterinary sciences · 2025Article
- An Extracellular Vesicle (EV) Paper Strip for Rapid and Convenient Estimation of EV Concentration.Biosensors · 2025Article
- Decellularized tissue matrices hydrogels functionalized with extracellular vesicles promote macrophage reprogramming and neural stem cell differentiation for spinal cord injury repair.Journal of nanobiotechnology · 2025Article
- Extracellular Vesicles as Mediators and Potential Targets in Combating Cancer Drug Resistance.Molecules (Basel, Switzerland) · 2025Review
- Unveiling the immunomodulatory dance: endothelial cells' function and their role in non-small cell lung cancer.Molecular cancer · 2025Review
- Bevacizumab in ovarian cancer therapy: current advances, clinical challenges, and emerging strategies.Frontiers in bioengineering and biotechnology · 2025Review
- Molecular mechanisms of cisplatin resistance in ovarian cancer.Genes & diseases · 2024Review
- Beyond starving cancer: anti-angiogenic therapy.Journal of medical ultrasonics (2001) · 2024Review
- Recent advances to address challenges in extracellular vesicle-based applications for lung cancer.Acta pharmaceutica Sinica. B · 2024Review
- Extracellular vesicle-bound VEGF in oral squamous cell carcinoma and its role in resistance to Bevacizumab Therapy.Cancer cell international · 2024Article
- The molecular conversations of sarcomas: exosomal non-coding RNAs in tumor's biology and their translational prospects.Molecular cancer · 2024Review
- The Role of Intracellular and Extracellular Vesicles in the Development of Therapy Resistance in Cancer.Current pharmaceutical design · 2024Review
- Defining tropism and activity of natural and engineered extracellular vesicles.Frontiers in immunology · 2024Review
- Extracellular vesicle-based liquid biopsy biomarkers and their application in precision immuno-oncology.Biomarker research · 2023Review
- Extracellular vesicles in tumor angiogenesis and resistance to anti-angiogenic therapy.Cancer science · 2023Review
- The Roles of Extracellular Vesicles in the Progression of Renal Cell Carcinoma and Their Potential for Future Clinical Application.Nanomaterials (Basel, Switzerland) · 2023Review
- Review
- Primary cilia-mediated regulation of microglial secretion in Alzheimer's disease.Frontiers in molecular biosciences · 2023Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Shaolin MaDepartment 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.
Lingegowda S MangalaDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wen HuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
Emine BayaktarDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Akira YokoiDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wei HuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sunila PradeepDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Sanghoon LeeDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Paul D PiehowskiPacific Northwest National Laboratory, Richland, WA 99352, USA.
Alejandro Villar-PradosDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Sherry Y WuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Michael H McGuireDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Olivia D LaraDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cristian Rodriguez-AguayoCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Christopher J LaFargueDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nicholas B JenningsDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Karin D RodlandPacific Northwest National Laboratory, Richland, WA 99352, USA.
Tao LiuPacific Northwest National Laboratory, Richland, WA 99352, USA.
Vikas KundraDepartment of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Prahlad T RamDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sundaram RamakrishnanDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Gabriel Lopez-BeresteinCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Robert L ColemanDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anil K SoodDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USPacific Northwest National Laboratory · USMedical College of Wisconsin · USUniversity of Miami · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUPR/MDACC Partnership for Excellence in Cancer Research(Parent Grant U54 CA096297)U54CA096297 · NCI · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI Ilka C Rios · 2002 to 2026
$36.9MTumor Biology Research ProgramP30CA240139 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Daniel Bilbao · 2019 to 2026
$24.1MUPR/MDACC Partnership for Excellence in Cancer Research (Luis Segarra supplement)U54CA096300 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Larkin Strong · 2002 to 2026
$23.8MTRAINING OF ACADEMIC SURGICAL ONCOLOGISTST32CA009599 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Ashley M Holder, Jennifer A. Wargo · 1988 to 2026
$13.2MU.T. M. D. Anderson Cancer Center SPORE in Ovarian CancerP50CA217685 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2017 to 2021
$7.9MHarnessing the power of exosomes for non-coding RNA deliveryR35CA209904 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2017 to 2023
$5.0MThe Inhibition of HSP70 Induces Apoptosis in Pancreatic Cancer CellsR01CA124723 · NCI · UNIVERSITY OF MINNESOTA · PI GILBOA, ELI, RAMAKRISHNAN, SUNDARAM · 2007 to 2022
$4.5MNovel extra cellular RNA-based combinatorial RNA inhibition therapyUH3TR000943 · NCATS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CALIN, GEORGE A., LOPEZ-BERESTEIN, GABRIEL · 2015 to 2017
$3.2MTargeted therapeutics for ovarian cancer and its microenvironment - treatment and theoretical modelingU01CA213759 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOPEZ-BERESTEIN, GABRIEL · 2017 to 2021
$2.5MNCATS NIH HHS UH3 TR000943NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA240139NCI NIH HHS P50 CA217685NCI NIH HHS R01 CA124723NCI NIH HHS R35 CA209904NCI NIH HHS T32 CA009599NCI NIH HHS U01 CA213759NCI NIH HHS U54 CA096297NCI NIH HHS U54 CA096300
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.
Indexed as
AgedAnimalsBevacizumabCell Line, TumorCell ProliferationDisease Models, AnimalExtracellular VesiclesFemaleHumansMiceMice, NudeMiddle AgedNeovascularization, PathologicOvarian NeoplasmsProtein IsoformsSignal TransductionBevacizumabProtein IsoformsTetraspanin 30Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2angiogenesisbevacizumabCD63drug resistanceextracellular vesiclesVEGF
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.