Department of Molecular Biology, New Jersey 08544.
Lewis-Sigler Institute for Integrative Genomics, New Jersey 08544; Department of Chemistry, Princeton University, Princeton, New Jersey 08544.
J Biol Chem. 2010 Mar 26;285(13):9317-9321. doi: 10.1074/jbc.C110.104448. Epub 2010 Feb 5.
Breast cancer is the most common cancer type for women in the western world. Despite decades of research, the molecular processes associated with breast cancer progression are still inadequately defined. Here, we focus on the systematic alteration of metabolism by using the state of the art metabolomic profiling techniques to investigate the changes of 157 metabolites during the progression of normal mouse mammary epithelial cells to an isogenic series of mammary tumor cell lines with increasing metastatic potentials. Our results suggest a two-step metabolic progression hypothesis during the acquisition of tumorigenic and metastatic abilities. Metabolite changes accompanying tumor progression are identified in the intracellular and secreted forms in several pathways, including glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, fatty acid and nucleotide biosynthesis, and the GSH-dependent antioxidative pathway. These results suggest possible biomarkers of breast cancer progression as well as opportunities of interrupting tumor progression through the targeting of metabolic pathways.
在西方世界，乳腺癌是女性最常见的癌症类型。尽管经过了几十年的研究，但与乳腺癌进展相关的分子过程仍未得到充分定义。在这里，我们专注于通过使用最先进的代谢组学分析技术系统地改变代谢，研究正常小鼠乳腺上皮细胞向具有不同转移潜能的同源系列乳腺肿瘤细胞系进展过程中 157 种代谢物的变化。我们的研究结果表明，在获得致瘤和转移能力的过程中存在两步代谢进展假说。在肿瘤进展过程中，在几个途径中，包括糖酵解、三羧酸循环、磷酸戊糖途径、脂肪酸和核苷酸生物合成以及 GSH 依赖性抗氧化途径，鉴定出伴随肿瘤进展的代谢物的细胞内和分泌形式的变化。这些结果表明，乳腺癌进展的可能生物标志物以及通过靶向代谢途径中断肿瘤进展的机会。
