Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
Division of Medical Oncology, Genitourinary Cancer Program, University of Colorado School of Medicine, Aurora, CO, United States.
Biochem Biophys Res Commun. 2018 May 23;499(4):1004-1010. doi: 10.1016/j.bbrc.2018.04.038. Epub 2018 Apr 9.
The current paradigm in the development of new cancer therapies is the ability to target tumor cells while avoiding harm to noncancerous cells. Furthermore, there is a need to develop novel therapeutic options against drug-resistant cancer cells. Herein, we characterized the placental-derived stem cell (PLSC) exosomes (PLSC) and evaluated their anti-cancer efficacy in prostate cancer (PCa) cell lines. Nanoparticle tracking analyses revealed the size distribution (average size 131.4 ± 0.9 nm) and concentration of exosomes (5.23 × 10±1.99 × 10 per ml) secreted by PLSC. PLSC treatment strongly inhibited the viability of enzalutamide-sensitive and -resistant PCa cell lines (C4-2B, CWR-R1, and LNCaP cells). Interestingly, PLSC treatment had no effect on the viability of a non-neoplastic human prostate cell line (PREC-1). Mass spectrometry (MS) analyses showed that PLSC are loaded with 241 proteins and mainly with saturated fatty acids. Further, Ingenuity Pathway Analysis analyses of proteins loaded in PLSC suggested the role of retinoic acid receptor/liver x receptor pathways in their biological effects. Together, these results suggest the novel selective anti-cancer effects of PLSC against aggressive PCa cells.
目前,开发新癌症疗法的范例是能够靶向肿瘤细胞,同时避免对非癌细胞造成伤害。此外,还需要开发针对耐药癌细胞的新型治疗选择。本文中,我们对胎盘来源的干细胞(PLSC)外泌体(PLSC)进行了表征,并评估了其在前列腺癌(PCa)细胞系中的抗癌功效。纳米颗粒跟踪分析显示,PLSC 分泌的外泌体的尺寸分布(平均尺寸为 131.4±0.9nm)和浓度(5.23×10±1.99×10 个/ml)。PLSC 处理强烈抑制了恩扎鲁胺敏感和耐药的 PCa 细胞系(C4-2B、CWR-R1 和 LNCaP 细胞)的活力。有趣的是,PLSC 处理对非肿瘤性人类前列腺细胞系(PREC-1)的活力没有影响。质谱(MS)分析表明,PLSC 载有 241 种蛋白质,主要是饱和脂肪酸。此外,PLSC 中加载的蛋白质的 Ingenuity 通路分析表明,视黄酸受体/肝 X 受体通路在其生物学效应中起作用。总之,这些结果表明 PLSC 对侵袭性 PCa 细胞具有新型的选择性抗癌作用。