Dataset Information

Proteomics of Prostate Cancer Tissue Small Extracellular Vesicles Reveal Alteration of Metabolism

ABSTRACT: Prostate cancer (PCa) is a leading male malignancy worldwide, with metabolic reprogramming being a critical hallmark of its progression. Extracellular vesicles (EVs) derived from tissues directly reflect the tumor microenvironment, offering unique insights into cancer pathophysiology that are unattainable through cell line or biofluid-derived EVs. However, the functional roles of tissue-derived EVs in PCa metabolism remain poorly understood. Leveraging our expertise in murine PCa model establishment and EV isolation from prostate tissue, this study aimed to characterize functional differences between PCa and normal prostate tissue via proteomic analysis of tissue-derived small EVs (sEVs). We orthotopically implanted luciferase-labeled PCa cells into nude mice to establish an in situ PCa model, confirmed tumor formation via in vivo imaging, and harvested tissues after four weeks. sEVs were isolated using ultracentrifugation combined with an iodixanol density cushion and characterized by transmission electron microscopy, nanoparticle tracking analysis, and protein marker profiling. Proteomic analysis identified 28 upregulated and 24 downregulated proteins in PCa-derived sEVs compared to normal controls. Subcellular localization revealed enrichment in the cytoplasm, while pathway analysis highlighted significant involvement in metabolic processes, particularly glycolysis, amino acid biogenesis, carbon metabolism, and pyruvate metabolism. Our study establishes a robust method for isolating prostate tissue sEVs and provides the first evidence that PCa tissue-derived sEVs exhibit profound metabolic pathway alterations. These findings enhance our understanding of PCa progression mechanisms and may facilitate the development of novel diagnostic biomarkers and therapeutic strategies targeting metabolic dysregulation in PCa.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Prostate Gland

SUBMITTER: Ting Ding

LAB HEAD: Lijuan Yu

PROVIDER: PXD070089 | Pride | 2026-03-16

REPOSITORIES: Pride

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			Action	DRS
	HFX1_FPEP210040125-1A.raw	Raw
	HFX1_FPEP210040125-1A_PeptideGroups.txt	Txt
	HFX1_FPEP210040126-1A.raw	Raw
	HFX1_FPEP210040127-1A.raw	Raw
	HFX1_FPEP210040128-1A.raw	Raw

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Proteomics of Prostate Cancer Tissue Small Extracellular Vesicles Reveal Alteration of Metabolism.

Yu Lijuan L Ding Ting T Olofsson Bagge Roger R Zheng Lei L Hao Xiaoke X

Proteomics 20251117

Prostate cancer (PCa) is a leading male malignancy worldwide, with metabolic reprogramming being a critical hallmark of its progression. Extracellular vesicles (EVs) derived from tissues directly reflect the tumor microenvironment, offering unique insights into cancer pathophysiology that are unattainable through cell line or biofluid-derived EVs. However, the functional roles of tissue-derived EVs in PCa metabolism remain poorly understood. Leveraging our expertise in murine PCa model establish ...[more]

PMID: 41243699

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Project description:Prostate cancer (PCa) remains the malignancy with the highest morbidity in men (1). Although early-stage PCa usually causes no symptoms, cancer cells in prostate glands readily metastasize to bones, lymph nodes, lungs, and liver during PCa progression (2). Common strategies, including surgery, radiation therapy, and androgen-deprivation therapy, are promising treatments for early-stage PCa. However, advanced PCa still lacks effective therapeutic strategies (3-5). Thus, researchers are currently focused on inhibiting tumor progression to explore effective therapeutic strategies for PCa treatment (6, 7). Cancer-associated fibroblasts (CAFs), stromal cells derived from normal fibroblasts or epithelia, are one of the major cellular components in the tumor microenvironment (8, 9). Compared with normal fibroblasts, CAFs are activated with increased expression of key protein markers, such as α-SMA, FAP, vimentin and S100A4 protein (10, 11). In the tumor microenvironment, CAFs secrete various growth effectors or cytokines to the extracellular matrix and thereby promote tumor progression by directly enhancing cancer cell growth, angiogenic induction, the extracellular matrix modification, and tumor-promoting inflammatory mediation (11-14). Notably, CAFs could act as an immunosuppressive mediator for the formation of an immunosuppressive tumor environment by recruiting and activating multiple immune cells (15). As such, CAFs might be a potential target in anti-tumor immunotherapy (16, 17). Currently, increased research has focused on inhibiting the immunosuppressive function of prostate cancer-associated fibroblasts (prostate CAFs), which may suggest therapeutic strategies for PCa (18, 19). Polysaccharides from Lentinus edodes are known to exhibit potent anti-tumor and immunomodulatory functions. The anti-tumor mechanisms of L. edodes polysaccharides include regulating the innate immune system by mediating CAF function, preventing tumorigenesis, or directly killing tumor cells via cell cycle regulation or apoptotic induction (20-22). Our previous studies isolated a novel polysaccharide component (MPSSS) from L. edodes. We found the secretome of prostate CAFs treated with MPSSS could inhibit the proliferation of CD4+ and CD8+ T cells, which suggested that MPSSS could prevent the immunosuppressive function of prostate CAFs (22). However, although the secretome of MPSSS-treated prostate CAFs inhibit the proliferation of T cells, how the secretome of MPSSS-treated prostate CAFs affect PCa progression is still unclear. The secretome defines as all proteins secreted by the organism or living cells into the extracellular space, which consists of soluble proteins and extracellular vesicles (EVs) (23). The secretome of prostate CAFs pays vital roles in PCa tumor origination, progression (24, 25). Since EVs contains various molecules (proteins, RNA, DNA and lipid) (26), we speculate that soluble proteins and EVs of prostate CAFs might have the different influence on PCa cells. In this study, the secretome of prostate CAFs untreated/treated with MPSSS were separated into the high molecular weight secretome (>100 kD) and the low molecular weight secretome (3-100 kD) using 100 kD and 3kD MWCO memberane filtration to narrow down the range of active components. The high molecular weight secretome contained extracellular vesicles (EVs) and large soluble proteins, while the low molecular weight secretome contained the small soluble proteins. The secretome of prostate CAFs untreated/treated with MPSSS were used to explore the underlying function and molecular mechanism using quantitative proteomics and multiple biochemical approaches.