Cancer Cell Biology
Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion
Version of Record online: 24 OCT 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 5, pages 1030–1039, 1 March 2008
How to Cite
Coffelt, S. B., Waterman, R. S., Florez, L., Bentrup, K. H. z., Zwezdaryk, K. J., Tomchuck, S. L., LaMarca, H. L., Danka, E. S., Morris, C. A. and Scandurro, A. B. (2008), Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion. Int. J. Cancer, 122: 1030–1039. doi: 10.1002/ijc.23186
- Issue online: 24 DEC 2007
- Version of Record online: 24 OCT 2007
- Manuscript Accepted: 24 AUG 2007
- Manuscript Received: 18 APR 2007
- NIH. Grant Numbers: AI056229, 1P20RR20152-01
- Cancer Association of Greater New Orleans (CAGNO)
- ovarian cancer;
The role of the pro-inflammatory peptide, LL-37, and its pro-form, human cationic antimicrobial protein 18 (hCAP-18), in cancer development and progression is poorly understood. In damaged and inflamed tissue, LL-37 functions as a chemoattractant, mitogen and pro-angiogenic factor suggesting that the peptide may potentiate tumor progression. The aim of this study was to characterize the distribution of hCAP-18/LL-37 in normal and cancerous ovarian tissue and to examine the effects of LL-37 on ovarian cancer cells. Expression of hCAP-18/LL-37 was localized to immune and granulosa cells of normal ovarian tissue. By contrast, ovarian tumors displayed significantly higher levels of hCAP-18/LL-37 where expression was observed in tumor and stromal cells. Protein expression was statistically compared to the degree of immune cell infiltration and microvessel density in epithelial-derived ovarian tumors and a significant correlation was observed for both. It was demonstrated that ovarian tumor tissue lysates and ovarian cancer cell lines express hCAP-18/LL-37. Treatment of ovarian cancer cell lines with recombinant LL-37 stimulated proliferation, chemotaxis, invasion and matrix metalloproteinase expression. These data demonstrate for the first time that hCAP-18/LL-37 is significantly overexpressed in ovarian tumors and suggest LL-37 may contribute to ovarian tumorigenesis through direct stimulation of tumor cells, initiation of angiogenesis and recruitment of immune cells. These data provide further evidence of the existing relationship between pro-inflammatory molecules and ovarian cancer progression. © 2007 Wiley-Liss, Inc.