Title:	PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state
Authors:	Machado, Camila Maria Longo Skubal, Magdalena Haedicke, Katja Pittella-Silva, Fabio 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
metadata.dc.identifier.orcid:	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
metadata.dc.contributor.affiliation:	Universidade de Brasília, Faculdade de Ciências da Saúde, Laboratório de Patologia Molecular do Câncer
Assunto::	Próstata - câncer
Issue Date:	2022
Publisher:	bioRxiv preprint
Citation:	MACHADO, Camila Maria Longo et al. PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state. bioRxiv preprint, 2022. DOI: https://doi.org/10.1101/2022.02.25.482024.
Abstract:	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.
metadata.dc.description.unidade:	Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR)
DOI:	https://doi.org/10.1101/2022.02.25.482024
Appears in Collections:	Artigos publicados em periódicos e afins

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