ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P136 | DOI: 10.1530/endoabs.65.P136

Profiling of tissue inflammatory cytokine expression in a pancreatic neuroendocrine tumour mouse model identifies upregulation of the chemokine C-C motif ligand 2 (CCL2)

Omair Shariq, Kate Lines, Mark Stevenson & Rajesh Thakker

OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

Pancreatic neuroendocrine tumours (PNETs) may occur as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome, or as a non-familial isolated endocrinopathy. Current medical treatments for PNETs are largely ineffective in preventing tumour progression, so there is a need for better therapies, which will develop from an improved understanding of the mechanisms driving PNET tumorigenesis. Cytokine-driven inflammation has been implicated in the development and progression of various cancers, such as breast, colorectal and lung cancer; however, little is known about the role of inflammatory mediators in PNETs. We therefore analysed the pancreatic expression of 40 inflammatory cytokines in a conditional Men1 knockout mouse model, Men1L/L/RIP2-Cre, in which PNETs of the β cells develop by 6 months of age. All animal work was performed under an approved UK Home Office licence. Whole (tumour-laden) pancreas protein extracts were isolated from female (n = 5) mice aged between 7–10 months of age, and were interrogated with inflammation antibody arrays, consisting of 40 known murine inflammatory factors. Signal intensity values were compared with those of pancreata harvested from wild type female (n = 5) control mice. Of 40 potential candidates, only one chemokine, C-C motif ligand 2 (CCL2), was significantly upregulated in the pancreata of Men1L/L/RIP2-Cre mice (100% increase P<0.001), when compared to wild type mice. CCL2 (also known as monocyte chemoattractant protein-1, or MCP-1) is a potent chemokine involved in recruiting monocytes and macrophages to sites of inflammation via activation. CCL2 has also been shown to play a role in angiogenesis, proliferation and metastasis in various solid organ malignancies. Thus, our data suggests the possible role of CCL2 in the pathogenesis of PNETs and as a novel therapeutic target for these tumours.

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