Related Experiment Video
Updated: Jun 16, 2026
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Fas/CD95 deficiency in ApcMin/+ mice increases intestinal tumor burden
Hector Guillen-Ahlers1, Mark A Suckow, Francis J Castellino
1W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, United States of America.
Background:
Fas, a member of the tumor necrosis family, is responsible for initiating the apoptotic pathway when bound to its ligand, Fas-L. Defects in the Fas-mediated apoptotic pathway have been reported in colorectal cancer.
Methodology/Principal Findings:
In the present study, a variant of the Apc(Min/+) mouse, a model for the human condition, Familial Adenomatous Polyposis (FAP), was generated with an additional deficiency of Fas (Apc(Min/+)/Fas(lpr)) by cross-breeding Apc(Min/+) mice with Fas deficient (Fas(lpr)) mice. One of the main limitations of the Apc(Min/+) mouse model is that it only develops benign polyps. However, Apc(Min/+)/Fas(lpr) mice presented with a dramatic increase in tumor burden relative to Apc(Min/+) mice and invasive lesions at advanced ages. Proliferation and apoptosis markers revealed an increase in cellular proliferation, but negligible changes in apoptosis, while p53 increased at early ages. Fas-L was lower in Apc(Min/+)/Fas(lpr) mice relative to Apc(Min/+) cohorts, which resulted in enhanced inflammation.
Conclusions/Significance:
This study demonstrated that imposition of a Fas deletion in an Apc(Min/+) background results in a more aggressive phenotype of the Apc(Min/+) mouse model, with more rapid development of invasive intestinal tumors and a decrease in Fas-L levels.
Insights
Deficiency in Fas accelerates intestinal tumor development in a mouse model of Familial Adenomatous Polyposis (FAP). This Fas deletion leads to increased tumor burden, invasive lesions, and inflammation, highlighting Fas's role in tumor suppression.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Fas, a tumor necrosis factor family member, initiates apoptosis upon Fas ligand (Fas-L) binding.
- Defects in Fas-mediated apoptosis are implicated in colorectal cancer development.
Purpose of the Study:
- To investigate the impact of Fas deficiency on tumor development in the Apc(Min/+) mouse model of Familial Adenomatous Polyposis (FAP).
Main Methods:
- Generated Apc(Min/+)/Fas(lpr) mice by cross-breeding Apc(Min/+) and Fas-deficient (Fas(lpr)) mice.
- Analyzed tumor burden, lesion invasiveness, cellular proliferation, apoptosis markers, p53 levels, and Fas-L expression.
Main Results:
- Apc(Min/+)/Fas(lpr) mice exhibited significantly increased tumor burden and invasive lesions compared to Apc(Min/+) mice.
- Increased cellular proliferation and p53 expression were observed, with negligible changes in apoptosis.
- Reduced Fas-L levels and enhanced inflammation were noted in Apc(Min/+)/Fas(lpr) mice.
Conclusions:
- Fas deletion exacerbates the Apc(Min/+) mouse model phenotype, leading to more aggressive intestinal tumor development.
- The study indicates a role for Fas in suppressing intestinal tumor progression and highlights the interplay between Fas-L, inflammation, and tumor growth.
