title: Plasma proteome profiling of a mouse model of breast cancer identifies a set of up-regulated proteins in common with human breast cancer cells.
abstract: We have applied an in-depth quantitative proteomic approach, combining isotopic labeling extensive intact protein separation and mass spectrometry, for high confidence identification of protein changes in plasmas from a mouse model of breast cancer. We hypothesized that a wide spectrum of proteins may be up-regulated in plasma with tumor development and that comparisons with proteins expressed in human breast cancer cell lines may identify a subset of up-regulated proteins in common with proteins expressed in breast cancer cell lines that may represent candidate biomarkers for breast cancer. Plasma from PyMT transgenic tumor-bearing mice and matched controls were obtained at two time points during tumor growth. A total of 133 proteins were found to be increased by 1.5-fold or greater at one or both time points. A comparison of this set of proteins with published findings from proteomic analysis of human breast cancer cell lines yielded 49 proteins with increased levels in mouse plasma that were identified in breast cancer cell lines. Pathway analysis comparing the subset of up-regulated proteins known to be expressed in breast cancer cell lines with other up-regulated proteins indicated a cancer related function for the former and a host-response function for the latter. We conclude that integration of proteomic findings from mouse models of breast cancer and from human breast cancer cell lines may help identify a subset of proteins released by breast cancer cells into the circulation and that occur at increased levels in breast cancer.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. spitteri@fhcrc.org
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Pitteri
authors.forename: Vitor M
authors.initials: VM
authors.lastname: Faca
authors.forename: Karen S
authors.initials: KS
authors.lastname: Kelly-Spratt
authors.forename: A Erik
authors.initials: AE
authors.lastname: Kasarda
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lisa
authors.initials: L
authors.lastname: Newcomb
authors.forename: Alexei
authors.initials: A
authors.lastname: Krasnoselsky
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
authors.forename: Gina
authors.initials: G
authors.lastname: Choi
authors.forename: Matthew
authors.initials: M
authors.lastname: Fitzgibbon
authors.forename: Martin W
authors.initials: MW
authors.lastname: McIntosh
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kemp
authors.forename: Samir M
authors.initials: SM
authors.lastname: Hanash
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000510:Alpha-Globulins / Q000032:analysis; D000818:Animals; D001798:Blood Proteins / Q000032:analysis* / Q000302:isolation & purification; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000097:blood; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis / Q000097:blood; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000032:analysis / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013058:Mass Spectrometry; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000032:analysis / Q000097:blood; D040901:Proteomics / Q000379:methods*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D001798:Blood Proteins; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D005353:Fibronectins; D017874:Immediate-Early Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018975:Insulin-Like Growth Factor Binding Protein 5; D036341:Intercellular Signaling Peptides and Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071332:Lcn2 protein, mouse; D055513:Connective Tissue Growth Factor