Department of Cancer Physiology, Moffitt Cancer Center, Tampa, FL, USA.
Clin Exp Metastasis. 2022 Feb;39(1):15-19. doi: 10.1007/s10585-021-10101-2. Epub 2021 May 17.
There is abundant evidence that the phenotype of cells the tumor at the stromal interface is distinct from the tumor cells that are within the core. Molecular phenotyping of cells at the edge show that they express higher levels of proteins associated with elevated glycolytic metabolism, including GLUT-1, HIF-1, and CA-IX. An end product of glycolysis is the production of acid, and acidosis of tumors is strongly associated with increased metastatic potential across a wide variety of tumor types. The molecular machinery promoting this export of acid is being defined, with close collaboration between carbonic anhydrases, sodium dependent bicarbonate and monocarboxylate transporters. Neutralization of this acidity can prevent local invasion and metastasis, and this has led to the "acid-mediated invasion hypothesis" wherein export of acid from the tumor into the stroma leads to matrix remodeling, which can promote local invasion.
有大量证据表明，肿瘤间质界面处的细胞表型与核心内的肿瘤细胞明显不同。对边缘细胞的分子表型分析表明，它们表达高水平的与糖酵解代谢升高相关的蛋白，包括 GLUT-1、HIF-1 和 CA-IX。糖酵解的终产物是产生酸，肿瘤的酸中毒与多种肿瘤类型的转移潜能增加密切相关。促进这种酸输出的分子机制正在被定义，碳酸酐酶、钠离子依赖的碳酸氢盐和单羧酸转运体之间密切合作。中和这种酸度可以防止局部侵袭和转移，这导致了“酸介导的侵袭假说”，其中肿瘤内的酸被排出到基质中，导致基质重塑，从而促进局部侵袭。
