Recio-Aldavero Jorge, Parra-Gutiérrez Lorena, Muñoz-Moreno Laura, Román Irene D, Arenas María Isabel, Bajo Ana M
Unidad de Bioquímica y Biología Molecular, Departamento de Biología de Sistemas, Campus Científico-Tecnológico, Universidad de Alcalá, 28805 Alcalá de Henares, Spain.
Unidad de Biología Celular, Departamento de Biomedicina y Biotecnología, Campus Científico-Tecnológico, Universidad de Alcalá, 28805 Alcalá de Henares, Spain.
Cancers (Basel). 2025 Jan 4;17(1):141. doi: 10.3390/cancers17010141.
BACKGROUND/OBJECTIVES: Prostate cancer (PCa) is characterised by its progression to a metastatic and castration-resistant phase. Prostate tumour cells release small extracellular vesicles or exosomes which are taken up by target cells and can potentially facilitate tumour growth and metastasis. The present work studies the effect of exosomes from cell lines that are representative of the different stages of the disease on the tumoral phenotype of PC3 cells.
Exosomes were isolated by ultracentrifugation from human prostate epithelial cells (RWPE-1) and androgen-dependent PCa cells (LNCaP) and castration-resistant PCa cells (CRPC) with moderate (DU145) or high (PC3) metastatic capacity. The biophysical and biochemical properties of the exosomes were characterised as well as their effects on PC3 cell viability and migration.
The study of the exosomes of prostate cell lines shows heterogeneity in their size, presenting in some of them two types of populations; in both populations, a larger size in those derived from PC3 cells and a smaller size in those derived from non-tumourigenic prostate cells were detected. Differences were found in the physical properties of those derived from healthy and PCa cells, as well as between cells representative of the most aggressive stages of the disease. The highest gamma-glutamyl transferase (GGT) activity was observed in androgen-dependent cells and differences in the pro-metalloproteinases (MMP) activity were detected in healthy cells and in castration-resistant cells with moderate metastatic capacity with respect to PC3 cells. The treatment of PC3 cells with their own exosomes increased PC3 cell viability and migration.
Exosomes represent a promising field of research in the diagnosis, prognosis, and treatment of prostate cancer.
背景/目的：前列腺癌（PCa）的特征在于其进展为转移和去势抵抗阶段。前列腺肿瘤细胞释放小细胞外囊泡或外泌体，这些外泌体会被靶细胞摄取，并可能促进肿瘤生长和转移。本研究探讨了代表疾病不同阶段的细胞系来源的外泌体对PC3细胞肿瘤表型的影响。
通过超速离心从人前列腺上皮细胞（RWPE-1）、雄激素依赖性PCa细胞（LNCaP）以及具有中度（DU145）或高度（PC3）转移能力的去势抵抗性PCa细胞（CRPC）中分离外泌体。对外泌体的生物物理和生化特性进行了表征，并研究了它们对PC3细胞活力和迁移的影响。
对前列腺细胞系外泌体的研究表明，其大小存在异质性，其中一些呈现两种类型的群体；在这两种群体中，均检测到源自PC3细胞的外泌体尺寸较大，而源自非致瘤性前列腺细胞的外泌体尺寸较小。源自健康细胞和PCa细胞的外泌体在物理性质上存在差异，疾病最具侵袭性阶段的代表性细胞之间也存在差异。在雄激素依赖性细胞中观察到最高的γ-谷氨酰转移酶（GGT）活性，并且在健康细胞以及具有中度转移能力的去势抵抗性细胞与PC3细胞相比，检测到前基质金属蛋白酶（MMP）活性存在差异。用PC3细胞自身的外泌体处理可提高PC3细胞的活力和迁移能力。
外泌体在前列腺癌的诊断、预后和治疗方面代表了一个有前景的研究领域。
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