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Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Systematic high-content proteomic analysis reveals substantial immunologic changes in colorectal cancer
Uta Berndt1, Lars Philipsen, Sebastian Bartsch
1Department of Medicine, Division of Gastroenterology and Hepatology, Charité-Campus Virchow Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
Cancer Research
|February 5, 2008
Summary
This study reveals significant immune cell changes in colorectal cancer (CRC) tissue, identifying over 1,900 protein network motifs. These findings highlight altered T-cell activity and antigen presentation, crucial for understanding CRC and developing immunotherapies.
Area of Science:
- Immunology
- Oncology
- Proteomics
Background:
- The immune system's role in epithelial tumorigenesis is significant but not fully understood in colorectal cancer (CRC) pathogenesis.
- Immune function relies on the integrity of the protein network environment.
Purpose of the Study:
- To explore the toponome in colorectal cancer (CRC) mucosa using novel multiplexed robotic-imaging technology.
- To identify protein network motifs and immune cell alterations in CRC tissue compared to healthy and ulcerative colitis mucosa.
Main Methods:
- Multiplexed immunofluorescence microscopy (MELC) on structurally intact tissues from CRC, ulcerative colitis, and healthy colonic mucosa.
- High-content proteomic analysis to visualize dozens of proteins simultaneously and analyze the toponome.
Main Results:
- Identified 1,930 motifs distinguishing CRC from control tissue.
- Observed increased activated T cells (due to lack of bax, caspase-3, caspase-8), decreased CD4(+)CD25(+) T cells, and increased cytotoxic T cells in CRC.
- Noted increased activated human lymphocyte antigen (HLA)-DR(+) T cells, altered T-cell adhesion molecules (CD3(+)CD29(+), LFA-1, LFA-3), and increased natural killer and CD44(+) cells in CRC mucosa.
- Identified nuclear factor-kappaB as a regulator of apoptosis in these cell populations.
- Demonstrated extensive protein expression profile modifications in the lamina propria of CRC.
Conclusions:
- Topological proteomic analysis provides novel insights into the adaptive immune system's role in colorectal cancer (CRC).
- Findings may aid in developing new antitumor immunotherapy approaches for CRC.
