Pro-Tumorigenic Signaling Between Small Extracellular Vesicles of Cancer Cells and Bone Marrow-Derived Mesenchymal...

Area of Science:

• Oncology
• Cell Biology
• Extracellular Vesicles

Background:

• Retinoblastoma (Rb) is an eye tumor driven by genetic mutations.
• Metastasis, particularly to the bone marrow (BM), is a major challenge in Rb treatment.
• Tumor cell and bone marrow cell communication via extracellular vesicles is poorly understood.

Purpose of the Study:

• Investigate the role of tumor-derived sEVs (TD-sEVs) and BM-derived sEVs in Rb metastasis.
• Analyze the impact of sEVs on cell-to-cell crosstalk between Rb cells and BM mesenchymal stem cells (BM-MSCs).
• Characterize sEVs according to MISEV guidelines.

Main Methods:

• Confocal microscopy to assess sEV uptake and phenotypic changes.
• MTT, scratch, Transwell, colony, and sphere formation assays to evaluate cell function.
• Immunoblotting for stemness markers and dot blot assays for secretome analysis.

Main Results:

• Both Rb cells and BM-MSCs readily took up sEVs.
• TD-sEVs enhanced BM-MSC migration and induced myofibroblast differentiation without affecting viability.
• BM-MSC-derived sEVs increased Rb cell viability, migration, and stemness marker expression, altering secretomes.

Conclusions:

• sEVs mediate bidirectional communication between Rb cells and BM-MSCs.
• sEVs promote a pro-metastatic microenvironment in the bone marrow.
• Targeting sEV-mediated crosstalk may offer new therapeutic strategies for Rb metastasis.