Importantly, we further demonstrated that overexpressing PHD2 attenuated inflammation in colon cancer xenograft mice through weakening accumulation of myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs), as well as secretions of pro-inflammatory cytokines including G-CSF, TNF-α, IL-6, IL-8, IL-1β, and IL-4.
Increased IL-4 expression in human colorectal cancer tissue and growth of colon cancer cell lines implied that IL-4-induced Stat6-mediated tumorigenic signaling likely contributes to intestinal tumor progression in ApcMin/+ mice.
Importantly, CUEDC2 expression is almost undetectable in macrophages in human colon cancer, and this decreased CUEDC2 expression is associated with high levels of interleukin-4 and miR-324-5p.
Since the upregulation of IL-4 cytokine was recently demonstrated to constitute an important mechanism that protects the tumorigenic CD133+ cells from apoptosis, the potential benefits of standard chemotherapeutic treatments in combination with IL-4 inhibitors in the context of human colon carcinoma, are also discussed.
When the sub-analyses were carried out, the homozygotes for IL4 -588C>T or for Ex1-168G>A showed an increased risk for colon cancer only, with the odds ratios of 4 (95% CI 0.97-16.6; P-interaction=0.016 and 4.66 (95% CI 1.16-18.77; P-interaction=0.023), respectively.
We have tested the hypothesis that the vitamin A metabolite all-trans retinoic acid (RA) is required for the regulation of pIgR expression by the cytokines interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in HT-29 cells, a well-differentiated human epithelial cell line derived from a colonic carcinoma. pIgR expression is upregulated by IFN-gamma and IL-4 when HT-29 cells are grown in normal media, but this upregulation was significantly lower when cells were grown in vitamin A-depleted media.
The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo.