Massive Overexpression of Chitnase3-like 4 (YM2), CD30 and Immunoglobulin in LMP1 Induced Inflammation Associated Carcinogenesis

McLean, A., Tsimbouri, P. and Wilson, J.B. (2008) Massive Overexpression of Chitnase3-like 4 (YM2), CD30 and Immunoglobulin in LMP1 Induced Inflammation Associated Carcinogenesis. 13th International EBV Symposium, Guangzgou, China, 7-10 Nov 2008.

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Abstract

There is an increasing body of evidence linking chronic inflammation and cancer but the mechanistic connection is poorly understood and the mediators of inflammation immensely complex. Most cancers are accompanied by leukocyte infiltration (and nasopharyngeal carcinoma is no exception), which, contrary to the anticipated immune role, could be contributing to tumour development and progression. In order to explore key carcinogenic factors in EBV associated malignancy we have studied a transgenic mouse model of epithelial carcinogenesis in which the Epstein-Barr virus oncogene LMP1 (CAO variant) is expressed. The preneoplastic skin, demonstrating hyperplasia and erosive dermatitis, was found to be inflamed with a mixed infiltrate involving T-cells (including NKT cells), mast cells and neutrophils. Several inflammatory factors were upregulated in the affected tissue, notably CD30 and CD30L, also MIP2, MIP3, CRG2/IP-10 and IL-1β and particularly the B-cell attractant CXCL13 (BLC). Immunoglobulin deposition was found to occur as the pathology worsens indicating a B-cell involvement. The role of mature T- and/or B-lymphocytes in the advancing pathology was demonstrated by their elimination, which limits the pathology to an early, benign stage. We have found that a chitinase-related protein, lacking enzymatic activity (termed YM2 or chitinase3-like4) is massively upregulated in the LMP1 expressing epidermis. We will present evidence to suggest that YM2 may be acting in concert with immunoglobulin to promote inflammation. The repeated identification of over-expressed chitinase-like proteins in models of inflammatory disorders suggests a crucial role for this protein family in inflammation. Factors which promote or sustain chronic inflammation may prove to be effective chemotherapeutic targets and their identification is therefore an important prerequisite. In this model LMP1 is the inducing factor and its effect upon and purturbation of immune system cells (of both innate and adaptive systems) leading to an inflamed state may augment its oncogenic activity in the development of EBV associated carcinoma.

Item Type:Conference or Workshop Item
Status:Published
Refereed:No
Glasgow Author(s) Enlighten ID:Tsimbouri, Dr Monica and Wilson, Professor Joanna
Authors: McLean, A., Tsimbouri, P., and Wilson, J.B.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Life Sciences
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