Department of Pathology, Democritus University of Thrace Medical School, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Cancer Biol Ther. 2012 Nov;13(13):1284-9. doi: 10.4161/cbt.21785. Epub 2012 Aug 16.
Tumor-associated stroma (TAS) is not simply a supporting element for cancer cells, but plays an important role in tumor growth, invasion and metastasis. Changes on the level of stromal constituents, such as loss of Caveolin-1 and increased thymidine phosphorylase (TP) expression, have been associated with tumor aggressiveness. The mutual cooperation between stromal fibroblasts and cancer cells is another distinguishing feature, which has recently emerged. In this investigation, both the loss of Caveolin-1 and the increased TP expression in the prostatic TAS was associated with high Gleason score (p = 0.0002 and 0.003, respectively); the two proteins were acting both independently and synergistically. In addition, TP was significantly associated with high stromal Ki-67 (MIB1) proliferation index (p = 0.03). Analysis of the metabolic interactions between stromal and epithelial elements showed that, while prostatic cancer cells express principally (> 91%) lactate dehydrogenase-5 (LDH-5) (anaerobic metabolism), the tumor-associated fibroblasts/myofibroblasts (TAFs) express largely (67.8%) LDH-1 (aerobic metabolism)-the terms TAFs and TAS are used interchangeably. These two isoenzyme pathways act complementary; the LDH-5 pathway converts pyruvate to lactate, whereas the LDH-1 enzyme system utilizes the secreted metabolite lactate to produce pyruvate, essential for continuous energy supply to tumor cells. Monocarboxylate transporter-1 (MCT-1)-the main facilitator of lactate uptake in tumor cells, was expressed exclusively in prostate cancer cells and related directly to LDH-5 overexpression. These findings support and extend our previous studies on energy recycling between the aerobic stroma and the anaerobic cancer cells within the framework of Warburg effect.
肿瘤相关基质（TAS）不仅仅是癌细胞的支持元素，而且在肿瘤生长、侵袭和转移中发挥着重要作用。基质成分水平的变化，如 Caveolin-1 的缺失和胸苷磷酸化酶（TP）表达的增加，与肿瘤的侵袭性有关。基质成纤维细胞和癌细胞之间的相互合作是另一个区别特征，最近已经出现。在这项研究中，前列腺 TAS 中 Caveolin-1 的缺失和 TP 表达的增加均与高 Gleason 评分相关（p=0.0002 和 0.003）；这两种蛋白既独立又协同作用。此外，TP 与高基质 Ki-67（MIB1）增殖指数显著相关（p=0.03）。对基质和上皮细胞之间代谢相互作用的分析表明，虽然前列腺癌细胞主要表达（>91%）乳酸脱氢酶-5（LDH-5）（无氧代谢），但肿瘤相关成纤维细胞/肌成纤维细胞（TAFs）主要表达（67.8%）乳酸脱氢酶-1（有氧代谢）——术语 TAFs 和 TAS 可互换使用。这两种同工酶途径相互补充；LDH-5 途径将丙酮酸转化为乳酸，而 LDH-1 酶系统利用分泌的代谢物乳酸产生丙酮酸，这对肿瘤细胞持续的能量供应至关重要。单羧酸转运蛋白-1（MCT-1）——肿瘤细胞摄取乳酸的主要促进剂，仅在前列腺癌细胞中表达，与 LDH-5 的过度表达直接相关。这些发现支持并扩展了我们之前关于有氧基质和无氧癌细胞之间能量回收的研究，这是在沃伯格效应的框架内进行的。
