title: Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts.
abstract: BACKGROUND
  Cathelicidin (LL-37 in humans and mCRAMP in mice) represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors.
  
  
  METHODS
  We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial-mesenchymal transition (EMT) of colon cancer cells and fibroblast-supported colon cancer cell proliferation.
  
  
  RESULTS
  Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-β1-induced EMT of colon cancer cells. Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer cell proliferation mediated by media conditioned by human colonic CCD-18Co fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts. Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer cell proliferation.
  
  
  CONCLUSIONS
  Cathelicidin effectively inhibits colon cancer development by interfering with EMT and fibroblast-supported colon cancer cell proliferation.
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Ho
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA ; Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea.
authors.forename: Jun Hwan
authors.initials: JH
authors.lastname: Yoo
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Deanna Hoang-Yen
authors.initials: DH
authors.lastname: Tran
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Bakirtzi
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Bowei
authors.initials: B
authors.lastname: Su
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Diana Hoang-Ngoc
authors.initials: DH
authors.lastname: Tran
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Yuzu
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Ichikawa
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Hon Wai
authors.initials: HW
authors.lastname: Koon
keywords: colon cancer; epithelial–mesenchymal transition; fibroblasts