Journal
PROTEOMICS
Volume 7, Issue 24, Pages 4589-4600Publisher
WILEY
DOI: 10.1002/pmic.200700425
Keywords
dermis-based cell-trapped system; fibrosarcoma tumor cells; ICPL; quantitative proteornes
Funding
- NCI NIH HHS [U01 CA105345, R01-CA79820, CA 16672] Funding Source: Medline
- NCRR NIH HHS [U54 RR020843-03] Funding Source: Medline
- NIAID NIH HHS [R01-AI067395-01, P30-AI36214-12S1, R01-AI50150] Funding Source: Medline
- NIAMS NIH HHS [P30-AR050948] Funding Source: Medline
- NIEHS NIH HHS [ES07784] Funding Source: Medline
- PHS HHS [R21-R022754-01, R21-I58002-01] Funding Source: Medline
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The alterations of tumor proteome and/or in vivo secretome created by host-tumor cell interaction may be crucial factors for tumors to undergo progression or regression in a host system. Two UV-induced fibrosarcoma tumor cell lines (UV-2237 progressive cells and UV-2240 regressive cells) were used as models to address this issue. Hundreds of proteins including in vivo secretome have been identified and quantified via an isotope-coded protein label (ICPL) in conjunction with high-throughput NanoLC-LTQ MS analysis. A newly designed technology using a dermis-based cell-trapped system was employed to encapsulate and grow 3-D tumor cells. A tissue chamber inserted with a tumor cell-trapped dermis was implanted into mice to mimic the tumor microenvironment. The in vivo secretome created by host-tumor interaction was characterized from samples collected from tissue chamber fluids via ICPL labeling mass,spectometric analysis. Twenty-five proteins including 14-3-3 proteins, heat shock proteins, profilin-1, and a fragment of complement C3 with differential expression in proteomes of UV-2237 and UV-2240 cells were revealed. Three secreted proteins including myeloperoxidase, alpha-2-macroglobulin, and a vitamin D-binding protein have different abundances in the in vivo secretome in response to UV2237 and UV-2240 cells. Differential tumor proteomes and in vivo secretome were thus accentuated as potential therapeutic targets to control tumor growth.
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