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

Coffelt, S. B. , Tomchuck, S. L., Zwezdaryk, K. J., Danka, E. S. and Scandurro, A. B. (2009) 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. Molecular Cancer Research, 7(6), pp. 907-915. (doi: 10.1158/1541-7786.MCR-08-0326) (PMID:19491199) (PMCID:PMC2755540)

Abstract

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.

• Item Type: Articles
• Additional Information: Grant support: NIH 1P20RR20152-01.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Coffelt, Professor Seth
• Authors: Coffelt, S. B., Tomchuck, S. L., Zwezdaryk, K. J., Danka, E. S., and Scandurro, A. B.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1541-7786
• ISSN (Online): 557-3125
• Published Online: 06 February 2009