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文章:

去势抵抗性细胞来源外泌体的表征及其对转移表型的影响

Characterisation of Castration-Resistant Cell-Derived Exosomes and Their Effect on the Metastatic Phenotype

原文发布日期:4 January 2025

DOI: 10.3390/cancers17010141

类型: Article

开放获取: 是

 

英文摘要:

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. Methods: 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. Results: 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. Conclusion: Exosomes represent a promising field of research in the diagnosis, prognosis, and treatment of prostate cancer.

 

摘要翻译: 

背景/目的:前列腺癌(PCa)的特征在于其进展至转移性和去势抵抗阶段。前列腺肿瘤细胞释放的小型细胞外囊泡(外泌体)可被靶细胞摄取,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细胞系的外泌体对PC3细胞肿瘤表型的影响。方法:通过超速离心法从人前列腺上皮细胞(RWPE-1)、雄激素依赖性前列腺癌细胞(LNCaP)以及具有中度(DU145)或高度(PC3)转移能力的去势抵抗性前列腺癌细胞(CRPC)中分离外泌体。对外泌体的生物物理和生化特性及其对PC3细胞活力和迁移的影响进行了表征。结果:对前列腺细胞系外泌体的研究表明,其大小存在异质性,部分细胞系呈现两种群体类型;在这两种群体中,均检测到PC3细胞来源的外泌体尺寸较大,而非致瘤性前列腺细胞来源的外泌体尺寸较小。健康细胞与前列腺癌细胞来源的外泌体在物理特性上存在差异,代表疾病最具侵袭性阶段的细胞之间也存在差异。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,而健康细胞和具有中度转移能力的去势抵抗性细胞与PC3细胞相比,在前金属蛋白酶(MMP)活性方面存在差异。用PC3细胞自身的外泌体处理PC3细胞可增强其活力和迁移能力。结论:外泌体在前列腺癌的诊断、预后和治疗中代表了一个具有前景的研究领域。

 

原文链接:

Characterisation of Castration-Resistant Cell-Derived Exosomes and Their Effect on the Metastatic Phenotype

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