研究动态
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由前列腺癌患者血清中的外泌体对LNCaP和PC3细胞引发更具侵袭性的肿瘤表型。

Induction of more aggressive tumoral phenotypes in LNCaP and PC3 cells by serum exosomes from prostate cancer patients.

发表日期:2023 Aug 01
作者: Raquel Huertas-Lárez, Laura Muñoz-Moreno, Jorge Recio-Aldavero, Irene Dolores Román, María Isabel Arenas, Ana Blasco, Ángeles Sanchís-Bonet, Ana M Bajo
来源: INTERNATIONAL JOURNAL OF CANCER

摘要:

前列腺癌(PCa)是全球男性第二常见和第六致命的癌症。尽管其高发病率,我们对其病因以及疾病进展中所涉及分子机制的了解非常有限。近年来,有关外泌体在此过程中的潜在参与已被提出。因此,我们旨在研究从前列腺癌患者血清中分离得到的外泌体对与肿瘤侵袭性增强有关的多种细胞过程在两种前列腺癌细胞系(LNCaP-FGC和PC3)中的影响。外泌体通过过滤杆和超速离心法分离。使用特异性标记物的免疫检测证实了它们的存在,并通过动态光散射(DLS)分析了它们的大小分布。所得结果表明,无论肿瘤分级如何,来自前列腺癌患者的血清外泌体均增加了PC3细胞的迁移和LNCaP-FGC细胞的神经内分泌分化。前列腺癌血清外泌体还增强了这两种细胞系中与侵袭性和对化疗药物耐药性相关的酶的分泌,如细胞外基质金属蛋白酶2和9以及γ-谷氨酰转肽酶。总之,这些发现支持了肿瘤细胞释放的外泌体在前列腺癌进展中的关键参与。对观察到的变化涉及的分子机制进行的未来研究可以为该疾病提供关键信息,并有助于发现新的治疗靶点。© 2023作者。由John Wiley & Sons Ltd代表UICC出版的《国际癌症杂志》发布。
Prostate cancer (PCa) is the second most frequent and sixth most fatal cancer in men worldwide. Despite its high prevalence, our understanding of its etiology and the molecular mechanisms involved in the progression of the disease is substantially limited. In recent years, the potential participation of exosomes in this process has been suggested. Therefore, we aim to study the effect of exosomes isolated from the serum of patients with PCa on various cellular processes associated with increased tumor aggressiveness in two PCa cell lines: LNCaP-FGC and PC3. The exosomes were isolated by filtration wand ultracentrifugation. Their presence was confirmed by immunodetection of specific markers and their size distribution was analyzed by Dynamic Light Scattering (DLS). The results obtained demonstrated that serum exosomes from PCa patients increased migration of PC3 cells and neuroendocrine differentiation of LNCaP-FGC cells regardless of the grade of the tumor. PCa serum exosomes also enhanced the secretion of enzymes related to invasiveness and resistance to chemotherapeutics, such as extracellular matrix metalloproteases 2 and 9, and gamma-glutamyltransferase in both cell lines. Altogether, these findings support the pivotal participation of exosomes released by tumoral cells in the progression of PCa. Future studies on the molecular mechanisms involved in the observed changes could provide crucial information on this disease and help in the discovery of new therapeutic targets.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.