Oncotarget

Research Papers:

Lect2 deficiency is characterised by altered cytokine levels and promotion of intestinal tumourigenesis

Kirsty R. Greenow, Matthew Zverev, Stephanie May, Howard Kendrick, Geraint T. Williams, Toby Phesse and Lee Parry _

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Oncotarget. 2018; 9:36430-36443. https://doi.org/10.18632/oncotarget.26335

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Abstract

Kirsty R. Greenow1, Matthew Zverev1, Stephanie May1, Howard Kendrick1, Geraint T. Williams2, Toby Phesse1 and Lee Parry1

1European Cancer Stem Cell Research Institute, Cardiff School of Biosciences, Cardiff University, Cardiff, UK

2School of Medicine, Cardiff University, Cardiff, UK

Correspondence to:

Lee Parry, email: parryl3@cardiff.ac.uk

Keywords: Lect2; Wnt; colorectal cancer; inflammation; intestine

Received: December 04, 2017     Accepted: October 28, 2018     Published: November 23, 2018

ABSTRACT

Leukocyte cell-derived chemotaxin 2 (Lect2) is a chemokine-like chemotactic factor that has been identified as a downstream target of the Wnt signalling pathway. Whilst the primary function of Lect2 is thought to be in modulating the inflammatory process, it has recently been implicated as a potential inhibitor of the Wnt pathway. Deregulation of the Wnt pathway, often due to loss of the negative regulator APC, is found in ~80% of colorectal cancer (CRC). Here we have used the ApcMin/+Lect2−/− mouse model to characterise the role of Lect2 in Wnt-driven intestinal tumourigenesis. Histopathological, immunohistochemical, PCR and flow cytometry analysis were employed to identify the role of Lect2 in the intestine. The ApcMin/+Lect2−/− mice had a reduced mean survival and a significantly increased number of adenomas in the small intestine with increased severity. Analysis of Lect2 loss indicated it had no effect on the Wnt pathway in the intestine but significant differences were observed in circulating inflammatory markers, CD4+ T cells, and T cell lineage-specification factors. In summary, in the murine intestine loss of Lect2 promotes the initiation and progression of Wnt-driven colorectal cancer. This protection is performed independently of the Wnt signalling pathway and is associated with an altered inflammatory environment during Wnt-driven tumorigenesis.


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