Cell and Gene Therapy Laboratory, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece.
First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Sci Rep. 2021 Sep 6;11(1):17718. doi: 10.1038/s41598-021-96038-8.
Both HPV-positive and HPV-negative cervical cancers are associated with aberrant metabolism, although the oncogenic drivers remain elusive. Here we show the assessment of the metabolomic profiles of four distinct cervical cell lines, a normal and three cancer cell lines, one HPV-negative (C33A) and two HPV-positive (SiHa HPV16+, HeLa HPV18+), employing an ultra performance liquid chromatography and a high resolution mass spectrometry. Out of the total 462 metabolites, 248 to 326 exhibited statistically significant differences, while Random Forests analysis identified unique molecules for each cell line. The two HPV+ cell lines exhibited features of Warburg metabolism, consistent with the role of the HPV E6 protein. SiHa and HeLa cells displayed purine salvage pathway activity, while C33A cells revealed synthesis of cytidine, via a novel mechanism. These data document a highly dynamic HPV-specific rewiring of metabolic pathways occurring in cervical cancer. Therefore, this approach can eventually provide novel mechanistic insights into cervical carcinogenesis.
HPV 阳性和 HPV 阴性的宫颈癌均与代谢异常相关，但其致癌驱动因素仍难以捉摸。在这里，我们通过超高效液相色谱和高分辨质谱分析了四种不同的宫颈细胞系（正常细胞系和三种癌细胞系，即 HPV 阴性的 C33A 细胞系、HPV 阳性的 SiHa 细胞系[HPV16+]和 HeLa 细胞系[HPV18+]）的代谢组学图谱。在总共 462 种代谢物中，有 248 到 326 种表现出统计学上的显著差异，而随机森林分析则为每种细胞系确定了独特的分子。这两种 HPV+细胞系表现出沃伯格代谢的特征，这与 HPV E6 蛋白的作用一致。SiHa 和 HeLa 细胞显示出嘌呤补救途径的活性，而 C33A 细胞则通过一种新的机制显示出胞苷的合成。这些数据记录了 HPV 特异性代谢途径在宫颈癌中发生的高度动态重排。因此，这种方法最终可以为宫颈癌的发生机制提供新的见解。
