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

被引:98
作者
Coffelt, Seth B. [1 ]
Waterman, Ruth S. [2 ]
Florez, Luisa [3 ]
zu Bentrup, Kerstin Honer [1 ]
Zwezdaryk, Kevin J. [1 ]
Tomchuck, Suzanne L. [1 ]
LaMarca, Heather L. [4 ]
Danka, Elizabeth S. [1 ]
Morris, Cindy A. [1 ]
Scandurro, Aline B. [1 ]
机构
[1] Tulane Univ, Dept Microbiol & Immunol, New Orleans, LA 70118 USA
[2] Tulane Univ, Dept Med, New Orleans, LA 70118 USA
[3] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词
hCAP-18; LL-37; ovarian cancer; inflammation;
D O I
10.1002/ijc.23186
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The role of the pro-inflammatory peptide, LL-37, and its proform, 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-1.8/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. (c) 2007 Wiley-Liss, Inc.
引用
收藏
页码:1030 / 1039
页数:10
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