Palviainen Mari, Laukkanen Kirsi, Tavukcuoglu Zeynep, Velagapudi Vidya, Kärkkäinen Olli, Hanhineva Kati, Auriola Seppo, Ranki Annamari, Siljander Pia
EV group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00790 Helsinki, Finland.
CURED, Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, 00790 Helsinki, Finland.
Cancers (Basel). 2020 Nov 6;12(11):3292. doi: 10.3390/cancers12113292.
Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer.
癌症会改变细胞代谢。这些变化如何在癌症来源的细胞外囊泡(EVs)的代谢物货物中体现,目前仍知之甚少。为了探究这些变化,通过差速超速离心法从前列腺、皮肤T细胞淋巴瘤(CTCL)、结肠癌细胞系中分离出EVs,并从其对应的非癌细胞中分离出对照EVs,然后通过纳米颗粒跟踪分析(NTA)、电子显微镜(EM)、蛋白质免疫印迹法和液相色谱 - 质谱联用(LC - MS)进行分析。尽管通过NTA和蛋白质免疫印迹法观察到癌源性和非癌源性细胞衍生的EVs之间存在细微差异,但在它们的代谢物货物中检测到的差异最为显著。与来自非癌细胞的EVs相比,癌症EVs中可溶性代谢物(如氨基酸和B族维生素)的水平升高。在所有三种癌症类型的EV样本中,脯氨酸和琥珀酸这两种代谢物的含量都有所升高。此外,前列腺和CTCL癌细胞系来源的EVs中叶酸和肌酐含量升高。总之,我们首次在体外证明,不同癌细胞代谢的改变反映在其EVs中常见的代谢物变化上。这些结果值得进一步研究这种代谢指纹在癌症中的意义和实用性。