Antimicrobial protein hCAP18/LL-37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells.

Johan D Heilborn, Margareta Frohm Nilsson, Clara I Chamorro Jimenez, Bengt Sandstedt, Niels Borregaard, Emma Tham, Ole E Sørensen, Günther Weber, Mona Ståhle
Author Information
  1. Johan D Heilborn: Unit of Dermatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

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.

MeSH Term

Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Blotting, Western
Breast Neoplasms
Cathelicidins
Cell Line
Cell Line, Tumor
Cell Proliferation
Epithelial Cells
Female
Humans
Immunoblotting
Immunohistochemistry
In Situ Hybridization
Inflammation
Leukocytes
Middle Aged
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Peptides
Pertussis Toxin
Phosphorylation
Transfection
Transgenes
Up-Regulation

Chemicals

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Cathelicidins
Peptides
Pertussis Toxin
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3

Word Cloud

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