title: Discovery of cancer biomarkers through the use of mouse models.
abstract: Although our understanding of the molecular pathogenesis of common types of cancer has improved considerably, the development of effective strategies for cancer diagnosis and treatment have lagged behind. Mouse models of cancer potentially represent an efficient means for uncovering diagnostic markers as genetic alterations associated with human tumors can be engineered in mice. In addition, defined stages of tumor development, breeding conditions, and blood sampling can all be controlled and standardized to limit heterogeneity. Alternatively human cancer cells can be injected into mice and tumor development monitored in xenotransplants. Mouse-based studies promise to elucidate a repertoire of protein changes that occur in blood and biological fluids during tumor development. This is illustrated in a study in which we have applied a three-dimensional intact protein analysis system (IPAS) to elucidate detectable protein changes in serum from immunodeficient mice with lung xenografts from orthotopically implanted human A549 lung adenocarcinoma cells. With sufficiently detailed protein sequence identifications, the observed protein changes can be attributed to either the host mouse or the human tumor cells. It is noteworthy that the majority of increases identified have corresponded to relatively abundant serum proteins, some of which have previously been reported as increased in the sera of cancer patients. Proteomic studies of mouse models of cancer allow assessment of the range of changes in plasma proteins that occur with tumor development and may lead to the identification of potential cancer markers applicable to humans.
authors.affiliation: Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.forename: David E
authors.initials: DE
authors.lastname: Misek
authors.forename: David J
authors.initials: DJ
authors.lastname: Monsma
authors.forename: Craig P
authors.initials: CP
authors.lastname: Webb
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Kelli J
authors.initials: KJ
authors.lastname: Peterson
authors.forename: Michael
authors.initials: M
authors.lastname: Pisano
authors.forename: Gilbert S
authors.initials: GS
authors.lastname: Omenn
authors.forename: Samir M
authors.initials: SM
authors.lastname: Hanash
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger