title: Antimicrobial protein hCAP18/LL-37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells.
abstract: Human cathelicidin antimicrobial protein hCAP18/LL-37 is an effector molecule of the nonspecific innate immune system. hCAP18/LL-37 is present in leukocytes and is expressed in skin and other epithelia, where it is upregulated in association with inflammation and injury. In addition, antimicrobial proteins including cathelicidins have been proposed to play a role in the nonspecific defense against tumors. To assess its potential role in tumor host defense, we investigated the expression of hCAP18/LL-37 in a series of breast carcinomas. Unexpectedly, we found that hCAP18/LL-37 was strongly expressed in the tumor cells and not in the adjacent stroma. To test the hypothesis that hCAP18/LL-37 may provide a growth advantage for the tumor cells, we treated human epithelial cell lines with synthetic biologically active LL-37 peptide and found a significant increase in cell proliferation. In addition, transgenic expression of hCAP18 in 2 different human epithelial cell lines resulted in increased proliferation of both cell types. These findings do not support the hypothesis that LL-37 has an antitumor effect, but rather suggest that hCAP18/LL-37 may promote tumor cell growth in breast cancer.
authors.affiliation: Unit of Dermatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan D
authors.initials: JD
authors.lastname: Heilborn
authors.forename: Margareta Frohm
authors.initials: MF
authors.lastname: Nilsson
authors.forename: Clara I Chamorro
authors.initials: CI
authors.lastname: Jimenez
authors.forename: Bengt
authors.initials: B
authors.lastname: Sandstedt
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
authors.forename: Emma
authors.initials: E
authors.lastname: Tham
authors.forename: Ole E
authors.initials: OE
authors.lastname: Sørensen
authors.forename: Günther
authors.initials: G
authors.lastname: Weber
authors.forename: Mona
authors.initials: M
authors.lastname: Ståhle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D054804:Cathelicidins; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D037342:Pertussis Toxin / Q000378:metabolism; D010766:Phosphorylation; D014162:Transfection; D019076:Transgenes; D015854:Up-Regulation
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D010455:Peptides; D037342:Pertussis Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3