Related Experiment Video
Updated: Jun 16, 2026
06:31
Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
Epithelial interleukin-4 receptor expression promotes colon tumor growth
Felicitas L Koller1, Daniel G Hwang, E A Dozier
1Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Carcinogenesis
|February 24, 2010
Summary
Interleukin-4 receptor alpha (IL4Ralpha) promotes colon tumor growth by increasing cell proliferation. Targeting IL4Ralpha significantly reduced tumor formation in mouse models, suggesting its therapeutic potential in colon cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Inflammatory mediators are key targets for cancer therapy.
- Interleukin-4 receptor alpha (IL4Ralpha) is part of receptor complexes for IL4 and IL13, T helper 2 cytokines.
Purpose of the Study:
- To investigate the role of IL4Ralpha in colonic tumorigenesis.
- To evaluate IL4Ralpha as a potential therapeutic target in colon cancer.
Main Methods:
- Assessed IL4Ralpha protein expression in human colon adenocarcinomas.
- Examined IL4Ralpha function in human and murine colon tumor cell lines in vitro.
- Utilized orthotopic allograft and chemically induced colitis-associated cancer mouse models to assess in vivo effects of IL4Ralpha ablation or blockade.
Main Results:
- IL4Ralpha was expressed in human colon tumors and colon tumor cell lines.
- Exogenous ligand treatment increased proliferation of IL4Ralpha-expressing cells in vitro.
- IL4Ralpha gene ablation or systemic blockade reduced tumor formation, proliferation, and increased apoptosis in mouse models.
Conclusions:
- IL4Ralpha contributes to colon tumor formation, likely by directly promoting epithelial tumor cell proliferation.
- IL4Ralpha blockade shows therapeutic potential in colitis-associated colon cancer.
- Targeting IL4Ralpha is a promising strategy for colon cancer treatment.
Related Concept Videos
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
02:17The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
01:23Renewal of Intestinal Stem Cells
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the goblet,...