title: Dynamic metabolic transformation in tumor invasion and metastasis in mice with LM-8 osteosarcoma cell transplantation.
abstract: While extensive evidence indicates that tumor cells shift their global metabolic programs, the molecular details of the metabolic transformation in tumor invasion, progression, and metastasis remain largely unknown. Characterization of the time-dependent metabolic shift during the tumor invasion, development, and metastasis will describe an important aspect of tumor phenotypes and potentially allow us to design therapies that inhibit tumor cell movement. In this study, a metabonomic study was performed to characterize the global metabolic changes during the process of tumor invasion and metastasis to lung in a mouse model with subcutaneous transplantation of murine osteosarcoma cell line (LM8). The serum metabolic profiling revealed that many key metabolites in glycolysis and tricarboxylic acid (TCA) cycle, as well as most of the amino acids were elevated at rapidly growing stage of tumor, presumably resulting from a high energy demand and turnover of anabolic metabolism during the tumor cell proliferation. Serum levels of succinic acid and proline significantly increased (with fold change FC = 10.75 and 4.43, relative to controls) among all the metabolites in the third week. The serum metabolic profile of lung metastasis at week 4 was different from that at week 3, in that most of previously increased serum metabolites were found decreased, except for cholesterol and several free fatty acids, suggesting lowered carbohydrate and amino acids metabolism, but an elevated lipid metabolism associated with tumor metastasis.
authors.affiliation: Musculoskeletal Oncology Center, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Hua
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Tianlu
authors.initials: T
authors.lastname: Chen
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Chi
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Cai
authors.forename: Zhanxiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002952:Citric Acid Cycle; D008401:Gas Chromatography-Mass Spectrometry; D006019:Glycolysis; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D055432:Metabolomics; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology