Document Detail

Leucine leucine-37 uses formyl peptide receptor-like 1 to activate signal transduction pathways, stimulate oncogenic gene expression, and enhance the invasiveness of ovarian cancer cells.
MedLine Citation:
PMID:  19491199     Owner:  NLM     Status:  MEDLINE    
Emerging evidence suggests that the antimicrobial peptide, leucine leucine-37 (LL-37), could play a role in the progression of solid tumors. LL-37 is expressed as the COOH terminus of human cationic antimicrobial protein-18 (hCAP-18) in ovarian, breast, and lung cancers. Previous studies have shown that the addition of LL-37 to various cancer cell lines in vitro stimulates proliferation, migration, and invasion. Similarly, overexpression of hCAP-18/LL-37 in vivo accelerates tumor growth. However, the receptor or receptors through which these processes are mediated have not been thoroughly examined. In the present study, expression of formyl peptide receptor-like 1 (FPRL1) was confirmed on ovarian cancer cells. Proliferation assays indicated that LL-37 does not signal through a G protein-coupled receptor, such as FPRL1, to promote cancer cell growth. By contrast, FPRL1 was required for LL-37-induced invasion through Matrigel. The peptide stimulated mitogen-activated protein kinase and Janus-activated kinase/signal transducers and activators of transcription signaling cascades and led to the significant activation of several transcription factors, through both FPRL1-dependent and FPRL1-independent pathways. Likewise, expression of some LL-37-stimulated genes was attenuated by the inhibition of FPRL1. Increased expression of CXCL10, EGF, and PDGF-BB as well as other soluble factors was confirmed from conditioned medium of LL-37-treated cells. Taken together, these data suggest that LL-37 potentiates a more aggressive behavior from ovarian cancer cells through its interaction with FPRL1.
Seth B Coffelt; Suzanne L Tomchuck; Kevin J Zwezdaryk; Elizabeth S Danka; Aline B Scandurro
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-06-02
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  7     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-24     Completed Date:  2009-09-18     Revised Date:  2013-12-25    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  907-15     Citation Subset:  IM    
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MeSH Terms
Antimicrobial Cationic Peptides / biosynthesis,  genetics,  metabolism,  pharmacology*
Cell Line, Tumor
Flow Cytometry
Gene Expression Regulation, Neoplastic / drug effects*
MAP Kinase Signaling System / physiology*
Neoplasm Invasiveness
Ovarian Neoplasms / drug therapy,  genetics,  metabolism*,  pathology
RNA, Small Interfering / genetics
Receptors, Formyl Peptide / antagonists & inhibitors,  biosynthesis,  genetics,  metabolism*
Receptors, G-Protein-Coupled / metabolism
Receptors, Lipoxin / antagonists & inhibitors,  biosynthesis,  genetics,  metabolism*
Recombinant Proteins / pharmacology
Grant Support
1P20RR20152-01/RR/NCRR NIH HHS; P20 RR020152/RR/NCRR NIH HHS; P20 RR020152-010005/RR/NCRR NIH HHS; P20 RR020152-020005/RR/NCRR NIH HHS; P20 RR020152-037530/RR/NCRR NIH HHS; P20 RR020152-047687/RR/NCRR NIH HHS; P20 RR020152-056904/RR/NCRR NIH HHS
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/FPR2 protein, human; 0/RNA, Small Interfering; 0/Receptors, Formyl Peptide; 0/Receptors, G-Protein-Coupled; 0/Receptors, Lipoxin; 0/Recombinant Proteins; 143108-26-3/CAP18 lipopolysaccharide-binding protein

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