Buchumschlag

PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state

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Bibliographische Detailangaben
1. Verfasser: Machado, Camila Maria Longo
Publikationsdatum: 2022
Weitere Verfasser: Skubal, Magdalena, Haedicke, Katja, Silva, Fábio Pittella, Stater, Evan Paul, Silva, Thais Larissa Araujo de Oliveira, Costa, Erico Tosoni, Masotti, Cibele, Otake, Andreia Hanada, Andrade, Luciana Nogueira Sousa, Junqueira, Mara de Souza, Hsiao-Ting Hsu, Das, Sudeep, Mc Larney, Benedict, Pratt, Edwin Charles, Romin, Yevgeniy, Ning Fan, Manova-Todorova, Katia, Pomper, Martin, Grimm, Jan
Format: Article
Sprache: eng
Quelle: Repositório Institucional da UnB
Download full: https://repositorio.unb.br/handle/10482/45008
https://doi.org/10.1101/2022.02.25.482024
https://orcid.org/0000-0001-6122-1147
https://orcid.org/0000-0003-3446-5415
https://orcid.org/0000-0002-8825-5686
https://orcid.org/0000-0002-9644-7098
https://orcid.org/0000-0003-2679-1763
https://orcid.org/0000-0001-7413-4675
https://orcid.org/0000-0003-4462-0941
https://orcid.org/0000-0003-1303-1220
https://orcid.org/0000-0003-2735-1217
https://orcid.org/0000-0002-2404-6543
https://orcid.org/0000-0001-9393-204X
https://orcid.org/0000-0002-6165-7431
https://orcid.org/0000-0002-6054-6983
https://orcid.org/0000-0003-3649-6813
https://orcid.org/0000-0003-0915-6696
https://orcid.org/0000-0001-6753-3010
https://orcid.org/0000-0002-5282-9385
Zusammenfassung: Extracellular vesicles (EV) are comprised of vesicles budding from cell membranes and smaller intracellular vesicles shed by cells. EV play a role in remodeling the tumor microenvironment (TME) and support tumor progression. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with a carboxypeptidase function, frequently associated with poor clinical prognosis in prostate cancer (PCa). We previously identified an oncogenic PSMA signaling function in prostate cancer. Others demonstrated that EV isolated from the plasma of patients with high-grade PCa carry PSMA, but so far no pathophysiological effect has been associated with PSMA-bearing EV. Here we demonstrate that EV from PCa cells are able to transfer PSMA and its functionality to cells in the TME. The consequence of that EV-mediated PSMA transfer is an acute to long-term increased secretion of vascular endothelial growth factor-A (VEGF-A), angiogenin, pro-angiogenic and pro-lymphangiogenic mediators and increased 4E binding protein 1 (4EBP-1) phosphorylation in tumors. We compare EV from PCa cells with or without PSMA expression to address the role of PSMA-bearing EV in promoting pro-tumoral changes in the TME using classical molecular biology and novel molecular imaging approaches.

Online

https://repositorio.unb.br/handle/10482/45008
https://doi.org/10.1101/2022.02.25.482024
https://orcid.org/0000-0001-6122-1147
https://orcid.org/0000-0003-3446-5415
https://orcid.org/0000-0002-8825-5686
https://orcid.org/0000-0002-9644-7098
https://orcid.org/0000-0003-2679-1763
https://orcid.org/0000-0001-7413-4675
https://orcid.org/0000-0003-4462-0941
https://orcid.org/0000-0003-1303-1220
https://orcid.org/0000-0003-2735-1217
https://orcid.org/0000-0002-2404-6543
https://orcid.org/0000-0001-9393-204X
https://orcid.org/0000-0002-6165-7431
https://orcid.org/0000-0002-6054-6983
https://orcid.org/0000-0003-3649-6813
https://orcid.org/0000-0003-0915-6696
https://orcid.org/0000-0001-6753-3010
https://orcid.org/0000-0002-5282-9385

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