Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion

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. (2007) Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion. International Journal of Cancer, 122(5), pp. 1030-1039. (doi:10.1002/ijc.23186) (PMID:17960624)

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Abstract

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.

Item Type:Articles
Additional Information:Grant sponsor: NIH; Grant numbers: AI056229, 1P20RR20152-01; Grant sponsor: Cancer Association of Greater New Orleans (CAGNO).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coffelt, Dr Seth
Authors: 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.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:International Journal of Cancer
Publisher:Wiley
ISSN:00207136
ISSN (Online):1097-0215

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