Mass spectrometric proteomics profiles of in vivo tumor secretomes: Capillary ultrafiltration sampling of regressive tumor masses

Authors

  • Chun-Ming Huang Dr.,

    Corresponding author
    1. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA
    2. La Jolla Institute for Molecular Medicine, San Diego, CA, USA
    3. Division of Dermatology, Department of Medicine, University of California, San Diego, CA, USA
    • Rm2317A, 3350 La Jolla Village, San Diego, CA 92161, USA Fax: +1-858-642-1435
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  • Honnavara N. Ananthaswamy,

    1. Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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  • Stephen Barnes,

    1. Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA
    2. Comprehensive Cancer Center Mass Spectrometry Shared Facility, University of Alabama at Birmingham, Birmingham, AL, USA
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  • Yuliang Ma,

    1. The Burnham Institute, La Jolla, CA, USA
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  • Mikako Kawai,

    1. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA
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  • Craig A. Elmets

    1. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Abstract

Identification of in vivo secreted peptides/proteins (secretomes) in tumor masses has the potential to provide important biomarkers and therapeutic targets for cancer therapy. However, limitations of existing technologies have made obtaining these secretomes for analysis extremely difficult. Here we employed an in vivo sampling technique using capillary ultrafiltration (CUF) probes to collect secretomes directly from tumor masses. Mass spectrometric proteomics approaches were then used to identify the tumor secretomes. A UV-induced skin fibrosarcoma cell line (UV-2240) was subcutaneously injected into C3H/NeH mice, resulting in tumor masses that initially progressed, then regressed and eventually eradicated. We then implanted CUF probes into tumor masses at the progressive and regressive stage. Five secreted proteins (cyclophilin-A, S100A4, profilin-1, thymosin beta 4 and 10), previously associated with tumor progression, were identified from tumor masses at the progressive stage. Five secreted proteins including three protease inhibitors (fetuin-A, alpha-1 antitrypsin 1–6, and contrapsin) were identified from tumor masses at the regressive stage. The technique involving CUF probes linked to mass spectrometric proteomics reinforces systems biology studies of cell-cell interactions and is potentially applicable to the discovery of in vivo biomarkers in human disease.

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