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Updated: Aug 20, 2026
In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
Functional expression of TWEAK in human colonic adenocarcinoma cells
Tomoyuki Kawakita1, Katsuya Shiraki, Yutaka Yamanaka
1First Department of Internal Medicine, Mie University School of Medicine, 2-174 Eobashi, Tsu, Mie, Japan.
Abstract:
The TNF-like weak inducer of apoptosis (TWEAK) can induce diverse cellular responses, including cell death, inflammation, migration, and proliferation in various transformed cell lines. We investigated TWEAK sensitivity, TWEAK effects on nuclear factor-kappaB activation, and expression of TWEAK in the HT-29, LS180, SK-CO-1 and SW480 human colonic adenocarcinoma cell lines, all of which express the TWEAK receptor (Fn14). TWEAK alone induced cell death in SW480 cells and induced cell death of HT-29 cells after addition of IFN-gamma, actinomycin D or cycloheximide. TWEAK did not affect cell viability of LS-180 or SK-CO-1 cells. Activation of NF-kappaB was not obviously influenced by TWEAK in any of the cell lines. All four human colonic adenocarcinoma cell lines constitutively expressed TWEAK mRNA, protein and membrane-bound TWEAK antigen, as detected by RT-PCR, Western blotting and flow cytometry. Stimulation by an anticancer drug (camptothecin) augmented cell surface expression of TWEAK and all human colonic adenocarcinoma tissue samples studied (n=59) demonstrated positive staining for TWEAK antigen. Soluble TWEAK was detected in culture medium of these cell lines by ELISA and conditioned medium from SW480 cells incubated with anti-TWEAK antibody significantly inhibited endothelial cell tube formation in Matrigels. Thus, functional expression of TWEAK from human colonic adenocarcinoma cells may contribute to neovascularization.
Insights
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) impacts colon cancer cells differently. TWEAK expression in colon cancer cells may promote new blood vessel growth, contributing to tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The TNF-like weak inducer of apoptosis (TWEAK) pathway plays a role in various cellular processes, including cell death, inflammation, migration, and proliferation.
- TWEAK signaling is mediated through its receptor, Fn14, which is expressed on various cell types, including cancer cells.
Purpose of the Study:
- To investigate TWEAK sensitivity and its effects on nuclear factor-kappaB (NF-κB) activation in human colonic adenocarcinoma cell lines.
- To examine the expression of TWEAK in these cell lines and its potential role in tumor progression, specifically neovascularization.
Main Methods:
- Utilized RT-PCR, Western blotting, and flow cytometry to detect TWEAK expression (mRNA, protein, cell surface antigen) in HT-29, LS180, SK-CO-1, and SW480 cell lines.
- Assessed TWEAK-induced cell death and NF-κB activation in response to TWEAK stimulation, alone or in combination with other agents.
- Investigated the effect of conditioned medium from TWEAK-expressing cells on endothelial cell tube formation and analyzed TWEAK antigen in patient tumor samples.
Main Results:
- TWEAK induced cell death in SW480 cells and in HT-29 cells when combined with IFN-gamma, actinomycin D, or cycloheximide, but not in LS-180 or SK-CO-1 cells.
- NF-κB activation was not significantly influenced by TWEAK in any of the tested cell lines.
- All four colonic adenocarcinoma cell lines constitutively expressed TWEAK mRNA, protein, and cell surface antigen. TWEAK expression was augmented by camptothecin and detected in 59 patient tumor samples.
- Conditioned medium from SW480 cells inhibited endothelial cell tube formation, suggesting a role for soluble TWEAK in neovascularization.
Conclusions:
- Functional expression of TWEAK by human colonic adenocarcinoma cells contributes to neovascularization, potentially promoting tumor growth.
- TWEAK exhibits differential effects on cell viability across various colon cancer cell lines.
- The constitutive expression of TWEAK in colon cancer cells and tissues highlights its potential as a therapeutic target.
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