Metabolomic Changes Accompanying Transformation and Acquisition of Metastatic Potential in a Syngeneic Mouse Mammary Tumor Model
Metabolomic Changes Accompanying Transformation and Acquisition of Metastatic Potential in a Syngeneic Mouse Mammary Tumor Model
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DOI：
10.1074/jbc.c110.104448
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发表时间：
2010-03-26
影响因子：
4.8
通讯作者：
Kang, Yibin
中科院分区：
文献类型：
--
作者：
Lu, Xin;Bennet, Bryson;Kang, Yibin
乳腺癌是西方世界女性最常见的癌症类型。尽管经过数十年的研究，与乳腺癌进展相关的分子过程仍然没有得到充分的定义。在这里，我们通过使用最先进的代谢组学分析技术来研究正常小鼠乳腺上皮细胞向具有增加的转移潜力的一系列同基因乳腺肿瘤细胞系进展过程中 157 种代谢物的变化，从而重点关注代谢的系统改变。我们的结果提出了在获得致瘤和转移能力过程中的两步代谢进展假说。伴随肿瘤进展的代谢变化以细胞内和分泌形式在多种途径中被识别，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。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来中断肿瘤进展的机会。
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.