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Title: Characterization of the influence of the galactoside-binding protein Peanut Agglutinin on endothelial secretion of cytokines in cancer metastasis
Author: Wang, Weikun
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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Peanut agglutinin (PNA) is a dietary lectin which accounts for 0.15% of the total weight of peanut Arachis hypogaea. PNA is a galactoside-binding protein which binds highly specifically to the tumour-associated Thomsen-Friedenreich blood group antigen. Previous studies demonstrate that PNA rapidly enters the blood circulation after peanut ingestion. PNA interacts with oncofetal TF disaccharide on the transmembrane mucin protein MUC1, causing polarization of MUC1 and thus reveals functional cell surface adhesion molecules. Therefore, circulating PNA has potential effects by inducing cancer cell homotypic and heterotypic adhesion, cell survival and migration, thus potentially promoting cancer metastasis and resistance to anoikis. In addition, earlier studies from our group have shown that a human galactoside-binding galectin-3 also interacts with MUC1-TF potentially inducing cancer metastasis from vascular endothelium. It is also reported that circulating galectin-3 enhances cytokine secretion from endothelial cells, and this interaction is suggested to be responsible for the metastasis-promoting effect of galectin-3. This thesis further explores the PNA effect on endothelial secretion of metastasis-associated cytokines. The study presented here reports that PNA at a concentration similar to that found in the sera of people after eating 200g peanuts causes increase of IL-6 and MCP-1 secretion from both micro-vascular and macro-vascular endothelial cells. The PNA-induced cytokine secretion was found to enhance endothelial expression of several cell surface adhesion molecules, leading to increased cancer cellendothelial cell adhesion. The increased cytokine secretion is also shown to promote endothelial cell adhesion, proliferation and angiogenesis. The molecular mechanism of the PNA-induced cytokine secretion is also studied, and two cell surface adhesion molecules MCAM and PECAM were identified as major functional receptors of PNA. Moreover, siRNA-mediated suppression of MCAM and PECAM expression completely abolished the PNA-induced cytokine secretion from endothelial cells. This study also investigated the cell signaling involved in the potential pro-metastasis effect of PNA. The results from this study suggested that the actions of dietary PNA in cancer patients might have impacts on cancer growth and metastasis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral