Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors Journal Article
| Authors: | Machado, C. M. L.; Skubal, M.; Haedicke, K.; Silva, F. P.; Stater, E. P.; Silva, T. L. A. D. O.; Costa, E. T.; Masotti, C.; Otake, A. H.; Andrade, L. N. S.; Junqueira, M. D. S.; Hsu, H. T.; Das, S.; Mc Larney, B.; Pratt, E. C.; Romin, Y.; Fan, N.; Manova-Todorova, K.; Pomper, M.; Grimm, J. |
| Article Title: | Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors |
| Abstract: | Cell membrane-derived particles (Mp) are rounded membrane-enclosed particles that are shed from tumor cells. Mp are formed from tumor membranes and are capable of tumor targeting and immunotherapeutic agents because they share membrane homology with parental cells; thus, they are under consideration as a drug delivery vehicle. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein with enzymatic functionality, is highly expressed in Mp and extracellular vesicles (EV) from prostate cancer (PCa) with poor clinical prognosis. Although PSMA expression was previously shown in EV and Mp isolated from cell lines and from the blood of patients with high-grade PCa, no pathophysiological effects have been linked to PCa-derived Mp. Here, we compared Mp from PSMA-expressing (PSMA-Mp) and PSMA-non-expressing (WT-Mp) cells side by side in vitro and in vivo. PSMA-Mp can transfer PSMA and new phenotypic characteristics to the tumor microenvironment. The consequence of PSMA transfer to cells and increased secretion of vascular endothelial growth factor-A (VEGF-A), pro-angiogenic and pro-lymphangiogenic mediators, with increased 4E binding protein 1 (4EBP-1) phosphorylation. © 2023 Elsevier B.V. |
| Keywords: | angiogenesis; cell culture; tumors; diagnosis; urology; vascular endothelial growth factor; microenvironment; prostate cancers; diseases; drug delivery; extracellular; cells; vegf-a; membranes; psma; cell engineering; microenvironments; prostate-specific membrane antigens; angiogenin; psma-cell-membrane derived particles; prostate-specific membrane antigen-cell-membrane derived particle; vascular endothelial growth factor-a |
| Journal Title: | Journal of Controlled Release |
| Volume: | 364 |
| ISSN: | 0168-3659 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2023-12-01 |
| Start Page: | 312 |
| End Page: | 325 |
| Language: | English |
| DOI: | 10.1016/j.jconrel.2023.10.038 |
| PROVIDER: | scopus |
| PUBMED: | 37884210 |
| PMCID: | PMC10842212 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Jan Grimm -- Source: Scopus |
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