title: Quantitative proteomes and in vivo secretomes of progressive and regressive UV-induced fibrosarcoma tumor cells: mimicking tumor microenvironment using a dermis-based cell-trapped system linked to tissue chamber.
abstract: 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 spectrometric 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 UV-2237 and UV-2240 cells. Differential tumor proteomes and in vivo secretome were thus accentuated as potential therapeutic targets to control tumor growth.
authors.affiliation: Burnham Institute for Medical Research, La Jolla, CA, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Smith
authors.forename: Yu-Tsueng
authors.initials: YT
authors.lastname: Liu
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Chen
authors.forename: Cheng-Po
authors.initials: CP
authors.lastname: Huang
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhu
authors.forename: Honnavara N
authors.initials: HN
authors.lastname: Ananthaswamy
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Huang
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D020405:Dermis / Q000473:pathology* / Q000528:radiation effects; D005354:Fibrosarcoma / Q000473:pathology*; D007553:Isotope Labeling; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis* / Q000737:chemistry; D009195:Peroxidase / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D014466:Ultraviolet Rays
chemical_list: D048948:14-3-3 Proteins; D009363:Neoplasm Proteins; D020543:Proteome; D009195:Peroxidase