Extracellular Vesicles as Mediators of Nickel-Induced Cancer Progression

Area of Science:

• Environmental Toxicology
• Cell Biology
• Cancer Research

Background:

• Extracellular vesicles (EVs) are key mediators of intercellular communication and play roles in cancer progression.
• Nickel (Ni) is a human carcinogen, but the mechanisms of Ni-induced carcinogenesis are not fully understood.

Purpose of the Study:

• To investigate the role of extracellular vesicles (EVs) in nickel-induced carcinogenesis.
• To characterize the impact of nickel exposure on EV production and function.

Main Methods:

• Chronic nickel exposure was used to generate Ni-transformed cells (Ni-6W, Ni-3, HNi-4).
• EVs were isolated from Ni-exposed and control cells and their signatures analyzed.
• Cellular uptake, inflammatory responses, and epithelial-mesenchymal transition (EMT) induction by Ni-altered EVs were assessed.

Main Results:

• Nickel-exposed cells produced significantly more EVs compared to control cells.
• EVs from Ni-transformed cells were enriched in protein and RNA.
• Ni-altered EVs were preferentially taken up by epithelial and endothelial cells, inducing inflammation and coagulation markers.
• Prolonged exposure to Ni-altered EVs induced EMT in epithelial cells.

Conclusions:

• Nickel exposure alters EV biogenesis and function.
• Ni-altered EVs contribute to cancer progression by promoting inflammation, altering endothelial cell function, and inducing EMT.
• EVs represent a potential mechanism in nickel-induced carcinogenesis.