肿瘤微环境中的酸中毒和蛋白水解作用。
Acidosis and proteolysis in the tumor microenvironment.
机构信息
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
出版信息
Cancer Metastasis Rev. 2019 Jun;38(1-2):103-112. doi: 10.1007/s10555-019-09796-3.
Abstract
The glycolytic phenotype of the Warburg effect is associated with acidification of the tumor microenvironment. In this review, we describe how acidification of the tumor microenvironment may increase the invasive and degradative phenotype of cancer cells. As a template of an extracellular acidic microenvironment that is linked to proteolysis, we use the resorptive pit formed between osteoclasts and bone. We describe similar changes that have been observed in cancer cells in response to an acidic microenvironment and that are associated with proteolysis and invasive and metastatic phenotypes. This includes consideration of changes observed in the intracellular trafficking of vesicles, i.e., lysosomes and exosomes, and in specialized regions of the membrane, i.e., invadopodia and caveolae. Cancer-associated cells are known to affect what is generally referred to as tumor proteolysis but little direct evidence for this being regulated by acidosis; we describe potential links that should be verified.
摘要
沃伯格效应的糖酵解表型与肿瘤微环境的酸化有关。在这篇综述中，我们描述了肿瘤微环境的酸化如何增加癌细胞的侵袭和降解表型。我们以破骨细胞和骨之间形成的吸收陷窝为模板，描述了在酸性微环境下观察到的类似变化，这些变化与蛋白水解和侵袭转移表型有关。这包括对细胞内囊泡（即溶酶体和外泌体）运输以及膜的特殊区域（即侵袭伪足和 caveolae）观察到的变化的考虑。众所周知，癌症相关细胞会影响通常被称为肿瘤蛋白水解的过程，但很少有直接证据表明这种过程受到酸中毒的调节；我们描述了一些潜在的联系，这些联系应该得到验证。
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