Interferon-Alpha Decreases Cancer Stem Cell Properties and Modulates Exosomes in Malignant Melanoma

Area of Science:

• Oncology
• Cancer Stem Cell Biology
• Immunotherapy

Background:

• Malignant melanoma (MM) exhibits resistance due to cancer stem cell (CSC) subpopulations.
• High-dose interferon-alpha (IFN-α) is used for melanoma but has significant side effects.

Purpose of the Study:

• To evaluate the impact of low and high doses of IFN-α on melanoma CSCs.
• To assess IFN-α's effects on CSC stemness, migration, and tumor initiation.
• To investigate genomic and exosomal changes induced by IFN-α.

Main Methods:

• Analysis of CSC markers (ALDH activity, side population, surface markers).
• Assessment of clonogenicity, migration, and tumor initiation in vitro and in vivo.
• Genomic analysis (microRNA sequencing, microarrays) and exosome characterization (NanoSight, LC-HRMS metabolomics).

Main Results:

• Both low and high doses of IFN-α reduced CSC formation and stemness properties.
• IFN-α significantly decreased tumor initiation capacity in mice xenotransplants.
• IFN-α modulated gene/microRNA expression and exosomal metabolomics, impacting cancer processes.

Conclusions:

• Low-dose IFN-α demonstrates efficacy against melanoma CSCs, reducing their aggressiveness and tumor-forming potential.
• IFN-α influences key cancer pathways and exosome communication.
• Combining low-dose IFN-α with metabolic biomarker analysis may offer a novel clinical strategy for melanoma treatment.