A Proteomic Analysis of the Plasma Glycoproteins of a MCF-7 Mouse Xenograft: A Model System for the Detection of Tumor Markers

• DOI: 10.1021/pr7008516
• Publication Date: 2008-03-13T06:01:16Z
• Authors: Christina I. Orazine; Marina Hincapie; William S. Hancock; Maureen Hattersley; Jeff H. Hanke
• Keywords: Proteomics; 0303 health sciences; Ovariectomy; Molecular Sequence Data; Mammary Neoplasms, Experimental; Mice, Nude; Breast Neoplasms; Estrogens; Blood Proteins; Mice; Random Allocation; Tamoxifen; 03 medical and health sciences; Tandem Mass Spectrometry; Cell Line, Tumor; Biomarkers, Tumor; Animals; Humans; Female; Amino Acid Sequence; Chromatography, High Pressure Liquid; Glycoproteins

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.