Anna Testa,
Medical Resident,
Thomas Jefferson University; Internal Medicine Fellow, University of Tur
Anna Testa received her Medical degree from University of Turin, Italy, and is currently a Visiting Scholar at Thomas Jefferson University as part of her fellowship in Internal Medicine at University of Turin. Her work supported by the PCF-YI award in Dr. Languino’s lab focuses mainly on aVbeta3 in extracellular vesicles isolated from prostate cancer patients.
The AlphaV-Beta3 Integrin/NgR2 Complex is Up-regulated in Prostate Cancer Cell-derived EVs and Patient-derived EVs and Represents a Promising Therapeutic Target
Wednesday, 26 July 2023 at 17:00
Add to Calendar ▼2023-07-26 17:00:002023-07-26 18:00:00Europe/LondonThe AlphaV-Beta3 Integrin/NgR2 Complex is Up-regulated in Prostate Cancer Cell-derived EVs and Patient-derived EVs and Represents a Promising Therapeutic TargetExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando, FloridaSELECTBIOenquiries@selectbiosciences.com
The AlphaV-Beta3 integrin, known to promote growth and metastasis of several types of cancer, is highly expressed in neuroendocrine prostate cancer (NEPrCa). PrCa cell-derived small extracellular vesicles (sEVs) expressing AlphaV-Beta3 contribute to NEPrCa differentiation in recipient cells. AlphaV-Beta3 integrin upregulates NgR2, a glycosylphosphatidylinositol-anchored receptor, in NEPrCa cells. By investigating the impact of AlphaV-Beta3 expression in sEVs on downstream protein expression via proteomic analysis, we demonstrate that AlphaV-Beta3+ sEVs also show an up-regulation in NgR2 expression; furthermore, a down-regulation of typical effectors involved in apoptosis and necrosis and an up-regulation of tumor cell survival factors emerge, as compared to control sEVs. We also show that EVs isolated from metastatic castrate-resistant prostate cancer (mCRPC) patients plasma are enriched in AlphaV-Beta3 and NgR2. sEVs used in these experiments were isolated by density gradient and characterized by nanoparticle tracking analysis and immunoblotting. Additionally, by testing the effect of AlphaV-Beta3 inhibition in NEPrCa-patient derived xenografts (PDXs) using LM609, a monoclonal antibody (mAb) specific for AlphaV-Beta3, we demonstrate a significant reduction of tumor volume and weight in NE-PDXs carrying mice upon treatment with LM609. Our findings suggest that AlphaV-Beta3 integrin and NgR2 are key components of NEPrCa progression and represent a promising therapeutic target both in vitro and in vivo.
Add to Calendar ▼2023-07-26 00:00:002023-07-27 00:00:00Europe/LondonExtracellular Vesicles 2023: Technologies, Biomarker Cargo and DiagnosticsExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando, FloridaSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2023-07-26 17:00:002023-07-26 18:00:00Europe/LondonThe AlphaV-Beta3 Integrin/NgR2 Complex is Up-regulated in Prostate Cancer Cell-derived EVs and Patient-derived EVs and Represents a Promising Therapeutic TargetExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando, FloridaSELECTBIOenquiries@selectbiosciences.com
