Hakobyan Gohar, Davtyan Hasmik, Harutyunyan Kristine, Alexanyan Knarik, Amirkhanyan Yelizaveta, Gharibyan Anna L, Asatryan Liana, Tadevosyan Yuri
Laboratory of Regulation of Cellular Activity, Institute of Molecular Biology, National Academy of Sciences, 0014 Yerevan, Armenia.
Center of Oncology after V. Fanarjyan, Ministry of Health RA, 0052 Yerevan, Armenia.
Med Sci (Basel). 2018 Nov 23;6(4):105. doi: 10.3390/medsci6040105.
Phospholipids (PLs), key elements of cellular membranes, are regulated reciprocally with membrane proteins and can act as sensors for alterations in physiological or pathological states of cells including initiation and development of cancer. On the other hand, peripheral blood mononuclear cells (MNCs) play an important role in antitumor immune response by reacting to cancerous modifications in distant organs. In the current study, we tested the hypothesis that tumor initiation and development are reflected in the alteration pattern of the MNC PL component. We analyzed MNC membrane PL fractions in samples from healthy individuals and from patients with diverse types of cancers to reveal possible alterations induced by malignancy. Compared to healthy controls, the cancer samples demonstrated shifts in several membrane PL profiles. In particular, when analyzing cancer data pooled together, there were significantly higher levels in lysophosphatidylcholine, phosphatidylcholine, and phosphatidylethanolamine fractions, and significantly lower quantities in phosphatidylinositol, phosphatidylserine, and phosphatidic acid fractions in cancer samples compared to controls. The levels of sphingomyelins and diphosphatidylglycerols were relatively unaffected. Most of the differences in PLs were sustained during the analysis of individual cancers such as breast cancer and chronic lymphocytic leukemia. Our findings suggest the presence of a common pattern of changes in MNC PLs during malignancy.
磷脂(PLs)是细胞膜的关键成分,与膜蛋白相互调节,可作为细胞生理或病理状态改变的传感器,包括癌症的发生和发展。另一方面,外周血单核细胞(MNCs)通过对远处器官的癌变修饰做出反应,在抗肿瘤免疫反应中发挥重要作用。在本研究中,我们检验了一个假设,即肿瘤的发生和发展反映在MNC PL成分的改变模式中。我们分析了健康个体和不同类型癌症患者样本中的MNC膜PL组分,以揭示恶性肿瘤可能引起的改变。与健康对照相比,癌症样本在几种膜PL谱上出现了变化。特别是,在汇总分析癌症数据时,与对照相比,癌症样本中的溶血磷脂酰胆碱、磷脂酰胆碱和磷脂酰乙醇胺组分水平显著升高,而磷脂酰肌醇、磷脂酰丝氨酸和磷脂酸组分的含量显著降低。鞘磷脂和二磷脂酰甘油的水平相对未受影响。在对乳腺癌和慢性淋巴细胞白血病等个体癌症的分析过程中,PLs的大多数差异持续存在。我们的研究结果表明,恶性肿瘤期间MNC PLs存在共同的变化模式。