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The Influence of Melanoma Extracellular Vesicles on Benign Melanocytes: A Role for PRAME in Modulation of the Tumor

Xiaochen Liu1, Ralf Janknecht2, Sepideh Nikki Asadbeigi1

  • 1Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; Department of Dermatology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

The Journal of Investigative Dermatology
|November 28, 2024
PubMed

Insights

Preferentially expressed antigen in melanoma (PRAME) in extracellular vesicles promotes melanoma progression by altering benign melanocyte behavior. Targeting PRAME-loaded EVs may inhibit melanoma metastasis and improve therapy response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Melanoma is an aggressive skin cancer known for metastasis and therapy resistance.
  • Preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, is implicated in tumor progression.
  • Extracellular vesicles (EVs) mediate intercellular communication and play roles in cancer.

Purpose of the Study:

  • To investigate the role of PRAME in melanoma progression.
  • To determine PRAME's function within melanoma-derived EVs.
  • To assess the impact of PRAME-carrying EVs on benign melanocytes.

Main Methods:

  • Analysis of PRAME expression in melanoma cell lines, tissues, and patient plasma.
  • Isolation and characterization of PRAME from melanoma EVs.
  • Co-culture experiments with melanoma EVs and benign melanocytes.
  • PRAME gene knockout in melanoma cells.

Main Results:

  • PRAME is highly expressed in melanoma and detected in EVs.
  • Melanoma EVs transfer PRAME (protein and mRNA) to benign melanocytes.
  • PRAME transfer induces gene expression changes, increased proliferation, and malignant phenotype in melanocytes.
  • PRAME knockout diminishes EV-mediated protumorigenic effects on melanocytes.

Conclusions:

  • PRAME is actively secreted via EVs and drives melanoma progression.
  • PRAME in EVs facilitates intercellular communication, promoting a malignant phenotype.
  • Plasma EV-associated PRAME shows potential as a biomarker for melanoma monitoring.
  • Targeting PRAME-containing EVs presents a novel therapeutic strategy against melanoma metastasis.
Keywords:
CancerExtracellular vesicleMelanomaMicroenvironmentPRAME

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