Metabolomic changes accompanying transformation and acquisition of metastatic potential in a syngeneic mouse mammary tumor model.
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.
Department of Molecular Biology, New Jersey 08544.
Xin
X
Lu
Lewis-Sigler Institute for Integrative Genomics, New Jersey 08544; Department of Chemistry, Princeton University, Princeton, New Jersey 08544.
Bryson
B
Bennet
Department of Molecular Biology, New Jersey 08544.
Euphemia
E
Mu
Lewis-Sigler Institute for Integrative Genomics, New Jersey 08544; Department of Chemistry, Princeton University, Princeton, New Jersey 08544.
Joshua
J
Rabinowitz
Department of Molecular Biology, New Jersey 08544; Breast Cancer Program, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903. Electronic address: ykang@princeton.edu.
Yibin
Y
Kang
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D017077:Culture Media, Conditioned; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008324:Mammary Tumor Virus, Mouse / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis
D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D005978:Glutathione