title: Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion.
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.
authors.affiliation: Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA.
authors.forename: Seth B
authors.initials: SB
authors.lastname: Coffelt
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Waterman
authors.forename: Luisa
authors.initials: L
authors.lastname: Florez
authors.forename: Kerstin
authors.initials: K
authors.lastname: Höner zu Bentrup
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Zwezdaryk
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Tomchuck
authors.forename: Heather L
authors.initials: HL
authors.lastname: LaMarca
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Danka
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Morris
authors.forename: Aline B
authors.initials: AB
authors.lastname: Scandurro
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D015854:Up-Regulation; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins