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

Autor: Camila Maria Longo Machado, Magdalena Skubal, Katja Haedicke, Fabio Pittella Silva, Evan Paul Stater, Thais Larissa Araujo de Oliveira Silva, Erico Tosoni Costa, Cibele Masotti, Andreia Hanada Otake, Luciana Nogueira Sousa Andrade, Mara de Souza Junqueira, Hsiao-Ting Hsu, Sudeep Das, Benedict Mc Larney, Edwin Charles Pratt, Yevgeniy Romin, Ning Fan, Katia Manova-Todorova, Martin Pomper, Jan Grimm
Přispěvatelé: Universidade de Brasília, Faculdade de Ciências da Saúde, Laboratório de Patologia Molecular do Câncer
Rok vydání: 2022
Předmět:
Zdroj: Repositório Institucional da UnB
Universidade de Brasília (UnB)
instacron:UNB
DOI: 10.1101/2022.02.25.482024
Popis: 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.
Databáze: OpenAIRE
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