title: A proteomic analysis of the plasma glycoproteins of a MCF-7 mouse xenograft: a model system for the detection of tumor markers.
abstract: In this study, we report a plasma proteomic analysis of a mouse MCF7 xenograft, using a novel platform named M-LAC (multilectin affinity chromatography), in an attempt to identify putative serum biomarkers of tumor presence and response to therapy. The use of the M-LAC platform enabled us to focus on secreted proteins as well as remove interference from serum albumin and other nonglycosylated proteins. The study focused on the MCF7 human xenograft tumor model which enabled us to distinguish tumor proteins (human peptide sequences) from host-derived murine proteins, potentially discriminating tumor- versus supporting tissue-derived markers. A large set of murine proteins was identified in this study, including several signaling molecules such as EGFR, interleukin-6 receptor, protein-kinase C, and phosphatidylinositol kinase which changed in plasma levels relative to tumor-free animals. We also detected in the samples with maximal tumor growth a number of human tumor-derived proteins linked to cell signaling, immune response, and transcriptional regulation. This is the first report where tumor-derived peptides could be detected in the serum of a xenograft model. We conclude that the M-LAC approach may be used to detect plasma proteins of potential biological significance in tumor-bearing animals and warrants further study in terms of increasing the sensitivity of the method for the characterization of low level tumor markers and to explore the applicability of these markers for human studies.
authors.affiliation: Barnett Institute, Northeastern University, 341 Mugar Building, Boston, Massachusetts 02115, USA.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Orazine
authors.forename: Marina
authors.initials: M
authors.lastname: Hincapie
authors.forename: William S
authors.initials: WS
authors.lastname: Hancock
authors.forename: Maureen
authors.initials: M
authors.lastname: Hattersley
authors.forename: Jeff H
authors.initials: JH
authors.lastname: Hanke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010052:Ovariectomy; D040901:Proteomics / Q000379:methods*; D011897:Random Allocation; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry / Q000379:methods; D014357:Trypsin / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D004967:Estrogens; D006023:Glycoproteins; D013629:Tamoxifen; D014357:Trypsin