Mitkevich Vladimir Alexandrovich, Petrushanko Irina Yu, Makarov Alexander Alexander
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Front Pharmacol. 2019 Aug 16;10:922. doi: 10.3389/fphar.2019.00922. eCollection 2019.
Exogenous RNases are selectively toxic to tumor cells. The reasons for this selectivity are not quite clear and should be searched for in the properties that distinguish malignant from normal cells. During onco-transformation, cells acquire properties allowing them to adapt to the altered microenvironment, such as resistance to hypoxia, changes in intracellular pH, disruption of ion transport, reduced adhesion and increased mobility, and production of specific exosomes. These adaptation mechanisms distinguish malignant cells from normal ones and give them a competitive advantage, ensuring survival and spread in the organism. Here, we analyze if the directed cytotoxic effect of exogenous RNases is linked to the disruption of the adaptive potential of tumor cells and how it can be used in anticancer therapy.
外源性核糖核酸酶对肿瘤细胞具有选择性毒性。这种选择性的原因尚不完全清楚,应该从区分恶性细胞与正常细胞的特性中去寻找。在肿瘤转化过程中,细胞获得了使其能够适应改变的微环境的特性,例如对缺氧的抗性、细胞内pH值的变化、离子转运的破坏、黏附性降低和迁移性增加,以及特定外泌体的产生。这些适应机制将恶性细胞与正常细胞区分开来,并赋予它们竞争优势,确保其在机体内的存活和扩散。在此,我们分析外源性核糖核酸酶的定向细胞毒性作用是否与肿瘤细胞适应潜能的破坏有关,以及它如何应用于抗癌治疗。