TY - JOUR
T1 - Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors
AU - Machado, Camila M.L.
AU - Skubal, Magdalena
AU - Haedicke, Katja
AU - Silva, Fabio P.
AU - Stater, Evan P.
AU - Silva, Thais L.A.de O.
AU - Costa, Erico T.
AU - Masotti, Cibele
AU - Otake, Andreia H.
AU - Andrade, Luciana N.S.
AU - Junqueira, Mara de S.
AU - Hsu, Hsiao Ting
AU - Das, Sudeep
AU - Larney, Benedict Mc
AU - Pratt, Edwin C.
AU - Romin, Yevgeniy
AU - Fan, Ning
AU - Manova-Todorova, Katia
AU - Pomper, Martin
AU - Grimm, Jan
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Angiogenin
KW - Microenvironment
KW - PSMA
KW - PSMA-cell-membrane derived particles
KW - VEGF-A
UR - https://www.scopus.com/pages/publications/85175250496
U2 - 10.1016/j.jconrel.2023.10.038
DO - 10.1016/j.jconrel.2023.10.038
M3 - Article
C2 - 37884210
AN - SCOPUS:85175250496
SN - 0168-3659
VL - 364
SP - 312
EP - 325
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -