Proteomics of prostate cancer tissue small extracellular vesicles reveal alteration of metabolism

Prostate cancer is one of the most common cancers affecting men worldwide, and one of its key features is the way tumor cells reprogram their metabolism to support rapid growth. A team led by researchers from the University of Gothenburg took a closer look at how prostate cancer tissue communicates these metabolic changes through tiny particles called small extracellular vesicles.

Extracellular vesicles, or EVs, act like molecular messengers that carry proteins and other cargo from one cell to another. EVs taken directly from tissues can reveal far more about the tumor microenvironment than EVs collected from blood or cell cultures because they come straight from the source. However, the metabolic role of tissue derived EVs in prostate cancer has remained unclear.

To investigate this question, the team used a mouse model where human prostate cancer cells were implanted directly into the prostate. After confirming tumor growth, they collected both tumor and normal prostate tissues and isolated small extracellular vesicles using high precision centrifugation and density separation. With imaging tools and protein analyses, they confirmed that the vesicles were correctly isolated and intact.

Proteins distinguished in prostate tissue sEVs between control and PCa murine model

Details are in the caption following the image

(a) Diagram showing the number of differentially expressed proteins. (b) Volcano plot showing proteins differentially expressed. Red: increased expression; Green: decreased expression. (c) The subcellular localization of the differentially expressed proteins. (d) Bar chart showing KEGG enrichment pathways. (e) Bubble plot showing GO enrichment in Biological Process. (f) Bubble plot showing GO enrichment in Cellular Component. (g) Bubble plot showing GO enrichment in molecular function.

Proteomic analysis revealed major differences between cancer derived vesicles and those from normal prostate tissue. The cancer related vesicles showed 28 proteins that increased and 24 that decreased compared to controls. Many of these proteins were involved in metabolic pathways essential for cancer growth, including glycolysis, amino acid production, carbon metabolism, and pyruvate metabolism. These pathways help fuel the high energy demands of tumor cells.

This work provides the first clear evidence that prostate cancer tissue releases extracellular vesicles enriched with proteins linked to metabolic reprogramming. These findings not only improve our understanding of how prostate cancer progresses but also suggest that the proteins carried by these vesicles could eventually serve as early biomarkers or targets for new therapies aimed at blocking cancer metabolism.

Yu L, Ding T, Olofsson Bagge R, Zheng L, Hao X, (2025) Proteomics of Prostate Cancer Tissue Small Extracellular Vesicles Reveal Alteration of Metabolism. Proteomics e70081. [article]

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