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J Pathol Clin Res. 2021 Sep;7(5):495-506. doi: 10.1002/cjp2.222. Epub 2021 May 14.

Colonic epithelial cathelicidin (LL-37) expression intensity is associated with progression of colorectal cancer and presence of CD8.

The journal of pathology. Clinical research

Ross J Porter, Graeme I Murray, Abdo Alnabulsi, Matthew P Humphries, Jacqueline A James, Manuel Salto-Tellez, Stephanie G Craig, Ji M Wang, Teizo Yoshimura, Mairi H McLean

Affiliations

  1. Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
  2. School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
  3. Precision Medicine Centre of Excellence, The Patrick G Johnston Centre for Cancer Research, Queen's University, Belfast, UK.
  4. Integrated Pathology Programme, Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
  5. Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
  6. Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
  7. Division of Molecular & Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.

PMID: 33988317 PMCID: PMC8363930 DOI: 10.1002/cjp2.222

Abstract

Colorectal cancer (CRC) remains a leading cause of cancer mortality. Here, we define the colonic epithelial expression of cathelicidin (LL-37) in CRC. Cathelicidin exerts pleotropic effects including anti-microbial and immunoregulatory functions. Genetic knockout of cathelicidin led to increased size and number of colorectal tumours in the azoxymethane-induced murine model of CRC. We aimed to translate this to human disease. The expression of LL-37 in a large (n = 650) fully characterised cohort of treatment-naïve primary human colorectal tumours and 50 matched normal mucosa samples with associated clinical and pathological data (patient age, gender, tumour site, tumour stage [UICC], presence or absence of extra-mural vascular invasion, tumour differentiation, mismatch repair protein status, and survival to 18 years) was assessed by immunohistochemistry. The biological consequences of LL-37 expression on the epithelial barrier and immune cell phenotype were assessed using targeted quantitative PCR gene expression of epithelial permeability (CLDN2, CLDN4, OCLN, CDH1, and TJP1) and cytokine (IL-1β, IL-18, IL-33, IL-10, IL-22, and IL-27) genes in a human colon organoid model, and CD3

© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.

Keywords: LL-37; cathelicidin; colorectal cancer; lymphocytes; organoid

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