Abstract
Peroxisome Proliferator Activated Receptors (PPARs) are members of the superfamily of nuclear receptor transcription factor. While the roles of isotypes PPARα and PPARγ in colorectal cancer have been well studied, the role of PPARβ/Δ still remains controversial. The reason for the discrepancies remains unclear and several explanations have been put forth. One explanation for the contrary view is the heterogeneous tumor microenvironment. A tumor is made up of the cancerous epithelia, as well as stromal elements such as cancer-associated fibroblasts (CAFs). The role of PPARβ/Δ in CAFs is not well understood, and concomitantly on tumor progression is not easily determined. We first examined mRNA expression of PPARβ/Δ in murine intestinal tumor stroma. Laser-capture microdissected tumor stroma showed a statistical significant change in stromal PPARB expression upon tumor formation. Mouse carrying a stromal-specific deletion of PPARβ/Δ showed that these mutant mice demonstrated increased cancer survivability, with reduced tumor size and numbers compared to their wild-type littermates, confirming the importance of stromal-derived PPARβ/Δ in colorectal tumorigenesis. Preliminary observations also suggest that stromal PPARβ/Δ may be a potential target for adjunctive anti-tumor treatment.
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