Peppicelli Silvia, Bianchini Francesca, Calorini Lido
Department of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni, 50, 50134, Florence, Italy.
Cancer Metastasis Rev. 2014 Sep;33(2-3):823-32. doi: 10.1007/s10555-014-9506-4.
Tumors are ecosystems which develop from stem cells endowed with unlimited self-renewal capability and genetic instability, under the effects of mutagenesis and natural selection imposed by environmental changes. Abnormal vascularization, reduced lymphatic network, uncontrolled cell growth frequently associated with hypoxia, and extracellular accumulation of glucose metabolites even in the presence of an adequate oxygen level are all factors contributing to reduce pH in the extracellular space of tumors. Evidence is accumulating that acidity is associated with a poor prognosis and participates actively to tumor progression. This review addresses some of the most experimental evidences providing that acidity of tumor environment facilitates local invasiveness and metastatic dissemination, independently from hypoxia, with which acidity is often but not always associated. Clinical investigations have also shown that tumors with acidic environment are associated with resistance to chemotherapy and radiation-induced apoptosis, suppression of cytotoxic lymphocytes, and natural killer cells tumoricidal activity. Therefore, new technologies for functional and molecular imaging as well as strategies directed to target low extracellular pH and low pH-adapted tumor cells might represent important issues in oncology.
肿瘤是一种生态系统,它由具有无限自我更新能力和基因不稳定性的干细胞在环境变化引起的诱变和自然选择作用下发展而来。异常的血管生成、减少的淋巴网络、常与缺氧相关的不受控制的细胞生长,以及即使在氧水平充足的情况下葡萄糖代谢产物的细胞外积累,都是导致肿瘤细胞外空间pH值降低的因素。越来越多的证据表明,酸性环境与预后不良相关,并积极参与肿瘤进展。本综述阐述了一些最新实验证据,这些证据表明肿瘤环境的酸性促进局部侵袭和转移扩散,与缺氧无关,虽然酸性常常但并非总是与缺氧相关。临床研究还表明,酸性环境的肿瘤与化疗耐药、辐射诱导的细胞凋亡、细胞毒性淋巴细胞的抑制以及自然杀伤细胞的杀肿瘤活性有关。因此,功能和分子成像新技术以及针对低细胞外pH值和适应低pH值肿瘤细胞的策略可能是肿瘤学中的重要问题。