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

SB Coffelt, RS Waterman, L Florez… - … journal of cancer, 2008 - Wiley Online Library
SB Coffelt, RS Waterman, L Florez, KH Bentrup, KJ Zwezdaryk, SL Tomchuck, HL LaMarca…
International journal of cancer, 2008Wiley Online Library
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 …
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. © 2007 Wiley‐Liss, Inc.
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