Antimicrobial protein hCAP18/LL‐37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells

Abstract

Human cathelicidin antimicrobial protein hCAP18/LL-37 is an effector molecule of the nonspecific innate immune system. hCAP18/LL-37 is present in leukocytes and is expressed in skin and other epithelia, where it is upregulated in association with inflammation and injury. In addition, antimicrobial proteins including cathelicidins have been proposed to play a role in the nonspecific defense against tumors. To assess its potential role in tumor host defense, we investigated the expression of hCAP18/ LL-37 in a series of breast carcinomas. Unexpectedly, we found that hCAP18/LL-37 was strongly expressed in the tumor cells and not in the adjacent stroma. To test the hypothesis that hCAP18/ LL-37 may provide a growth advantage for the tumor cells, we treated human epithelial cell lines with synthetic biologically active LL-37 peptide and found a significant increase in cell proliferation. In addition, transgenic expression of hCAP18 in 2 different human epithelial cell lines resulted in increased proliferation of both cell types. These findings do not support the hypothesis that LL-37 has an antitumor effect, but rather suggest that hCAP18/LL-37 may promote tumor cell growth in breast cancer.

Impaired IFN-α Production by Plasmacytoid Dendritic Cells Favors Regulatory T-cell Expansion That May Contribute to Breast Cancer Progression

“…In contrast, in breast tumors we observe that TApDC are strongly inhibited for their IFN-a production upon stimulation with exogenous TLR-L in vitro, in agreement with a previous study in head and neck cancer (16) and our recent work in ovarian carcinoma (24). As (i) tumors have been shown to express LL37 (25) and (ii) endogenous danger signals such as self-nucleic acids (26) are released from dying tumor cells, it is tempting to speculate that, upon (LL37/self-nucleic acids) complexes recognition TApDC might contribute to tumor immunosurveillance through type I IFNs production. This is consistent with the partially activated phenotype of breast TApDC.…”

The Human Cathelicidin LL-37 Modulates the Activities of the P2X7 Receptor in a Structure-dependent Manner

“…Growth-arrested NIH 3T3 cells were incubated for 24 h with LL-37 at peptide concentrations similar to those reported to promote keratinocyte proliferation (26,36). Cell numbers increased in a peptide concentration-dependent manner; the highest activity was achieved at 5 M LL-37.…”

Alarmins: awaiting a clinical response

“…Human cationic antimicrobial protein 18 (hCAP-18) is the only known member of the cathelicidin family in humans. The active peptide LL-37 is overexpressed in breast, lung, and ovarian tumors, probably functioning as an autocrine survival factor (91)(92)(93). It may also promote tumor growth through angiogenesis and recruitment of CD45 + cells (69).…”