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Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors

Camila M L Machado1, Magdalena Skubal2, Katja Haedicke2

  • 1Laboratorio de Investigação Médica de Medicina Nuclear-LIM-43, Departamento de Radiologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403911, Brazil; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|October 26, 2023
PubMed

Insights

Prostate cancer cell membrane particles (Mp) expressing PSMA can transfer PSMA and alter the tumor microenvironment, promoting angiogenesis and lymphangiogenesis. This highlights PSMA-Mp

Area of Science:

  • Oncology
  • Biotechnology
  • Molecular Biology

Background:

  • Cell membrane-derived particles (Mp) are shed from tumor cells and considered for drug delivery due to tumor-targeting capabilities.
  • Prostate-specific membrane antigen (PSMA) is highly expressed in Mp from prostate cancer (PCa) with poor prognosis.
  • Previous studies showed PSMA in Mp from PCa cell lines and patients, but without established pathophysiological effects.

Purpose of the Study:

  • To investigate the pathophysiological effects of PSMA-expressing Mp (PSMA-Mp) compared to PSMA-non-expressing Mp (WT-Mp).
  • To determine if PSMA-Mp can transfer PSMA and alter the tumor microenvironment.
  • To analyze the impact of PSMA-Mp on angiogenesis and lymphangiogenesis.

Main Methods:

  • In vitro and in vivo comparison of PSMA-Mp and WT-Mp.
  • Analysis of PSMA transfer from Mp to recipient cells.
  • Assessment of VEGF-A secretion and 4E-binding protein 1 (4EBP-1) phosphorylation.

Main Results:

  • PSMA-Mp successfully transferred PSMA and induced new phenotypic characteristics in the tumor microenvironment.
  • Increased secretion of vascular endothelial growth factor-A (VEGF-A) and other pro-angiogenic/pro-lymphangiogenic mediators was observed.
  • Elevated 4E-binding protein 1 (4EBP-1) phosphorylation was detected following PSMA transfer.

Conclusions:

  • PSMA-expressing Mp possess the ability to transfer PSMA and modify the tumor microenvironment.
  • PSMA-Mp contribute to pro-angiogenic and pro-lymphangiogenic processes, potentially influencing PCa progression.
  • These findings suggest a role for PSMA-Mp in the pathophysiology of prostate cancer.
Keywords:
AngiogenesisAngiogeninMicroenvironmentPSMAPSMA-cell-membrane derived particlesVEGF-A

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