Increased cathelicidin LL-37 colonic expression is associated with tumor progression in colorectal cancer

Colorectal cancer (CRC) remains a major global health challenge, with increasing incidence and limited treatment options. The antimicrobial peptide cathelicidin (LL-37) has been implicated in both tumorigenic and tumor-suppressive roles, but its precise function in CRC progression remains unclear. This study investigates the LL-37 expression in CRC and its association with key molecular pathways, including vitamin D signaling and G protein-coupled receptors (GPCRs). We analyzed LL-37 mRNA expression in 25 CRC tissue samples and matched healthy colonic mucosa using quantitative real-time PCR. Additionally, we assessed the expression of potential LL-37 target receptors, including formyl peptide receptor 2 (FPR2), toll-like receptors (TLR3, TLR4), CXC chemokine receptor 2 (CXCR2), and mas-related gene X2 (MrgX2). The correlation between LL-37 expression and clinicopathological factors, including tumor stage and nodal metastases, was also evaluated. LL-37 expression was significantly upregulated in CRC tissues compared to normal mucosa (p<0.001), with higher expression in advanced-stage CRC (AJCC stage III) and tumors with nodal metastases (p=0.006). Molecular analysis revealed significantly increased FPR2 expression and reduced TLR3 expression in CRC tissue, suggesting their involvement in tumor progression. Our findings suggest a role for LL-37 in CRC progression, potentially mediated through FPR2 activation and TLR3 suppression. The observed discrepancies in LL-37 function across studies highlight its complex, context-dependent role in tumor biology. Further research is needed to elucidate the mechanistic basis of LL-37 signaling and its potential as a therapeutic target in CRC.