Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma.
Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma.
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DOI：
10.1158/0008-5472.can-05-3260
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发表时间：
2006-01-15
期刊：
影响因子：
11.2
通讯作者：
Sivridis, E
中科院分区：
文献类型：
--
作者：
Koukourakis, MI;Giatromanolaki, A;Sivridis, E
了解肿瘤代谢对于开发抗癌疗法是重要的。结直肠腺癌的免疫组织化学评价显示，癌细胞具有共同的酶/转运蛋白活性，提示无氧代谢[高乳酸脱氢酶5（LDH 5）/缺氧诱导因子α s（HIF α s）]，具有高葡萄糖吸收和乳酸排出能力[高葡萄糖转运蛋白1（GLUT 1）/单羧酸转运蛋白（MCT 1）]。肿瘤相关的成纤维细胞表达的蛋白质参与乳酸盐吸收（高MCT 1/MCT 2），乳酸盐氧化（高LDH 1和低HIF α s/LDH 5），和葡萄糖吸收减少（低GLUT 1）。肿瘤相关内皮细胞的表达谱表明有氧代谢（高LDH 1和低HIF α s/LDH 5）、高葡萄糖吸收（高GLUT 1）和对乳酸摄入的抵抗（缺乏MCT 1）。这表明，新形成的基质和脉管系统表达互补的代谢途径，缓冲和回收厌氧代谢的产物，以维持癌细胞的存活。肿瘤存活和生长是因为它们能够将局部成纤维细胞和内皮细胞组织成一个和谐协作的代谢域。
Understanding tumor metabolism is important for the development of anticancer therapies. Immunohistochemical evaluation of colorectal adenocarcinomas showed that cancer cells share common enzyme/transporter activities suggestive of an anaerobic metabolism [high lactate dehydrogenase 5 (LDH5)/hypoxia-inducible factor alpha s (HIF alpha s)] with high ability for glucose absorption and lactate extrusion [high glucose transporter 1 (GLUT1)/monocarboxylate transporter (MCT1)]. The tumor-associated fibroblasts expressed proteins involved in lactate absorption (high MCT1/MCT2), lactate oxidation (high LDH1 and low HIF alpha s/LDH5), and reduced glucose absorption (low GLUT1). The expression profile of the tumor-associated endothelium indicated aerobic metabolism (high LDH1 and low HIF alpha s/LDH5), high glucose absorption (high GLUT1), and resistance to lactate intake (lack of MCT1). It is suggested that the newly formed stroma and vasculature express complementary metabolic pathways, buffering and recycling products of anaerobic metabolism to sustain cancer cell survival. Tumors survive and grow because they are capable of organizing the regional fibroblasts and endothelial cells into a harmoniously collaborating metabolic domain.