Wang, Weikun, Sindrewicz-Goral, Paulina, Chen, Chen, Duckworth, Carrie A 
ORCID: 0000-0001-9992-7540, Pritchard, David Mark ORCID: 0000-0001-7971-3561, Rhodes, Jonathan M ORCID: 0000-0002-1302-260X and Yu, Lu-Gang ORCID: 0000-0001-9641-3712
(2021)
Appearance of peanut agglutinin in the blood circulation after peanut ingestion promotes endothelial secretion of metastasis-promoting cytokines.
CARCINOGENESIS, 42 (8).
pp. 1079-1088.
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Abstract
Peanut agglutinin (PNA) is a carbohydrate-binding protein in peanuts that accounts for ~0.15% peanut weight. PNA is highly resistant to cooking and digestion and is rapidly detectable in the blood after peanut consumption. Our previous studies have shown that circulating PNA mimics the actions of endogenous galactoside-binding protein galectin-3 by interaction with tumour cell-associated MUC1 and promotes circulating tumour cell metastatic spreading. The present study shows that circulating PNA interacts with micro- as well as macro-vascular endothelial cells and induces endothelial secretion of cytokines MCP-1 (CCL2) and IL-6 in vitro and in vivo. The increased secretion of these cytokines autocrinely/paracrinely enhances the expression of endothelial cell surface adhesion molecules including integrins, VCAM and selectin, leading to increased tumour cell-endothelial adhesion and endothelial tubule formation. Binding of PNA to endothelial surface MCAM (CD146), via N-linked glycans, and subsequent activation of PI3K-AKT-PREAS40 signalling is here shown responsible for PNA-induced secretion of MCP-1 and IL-6 by vascular endothelium. Thus, in addition to its influence on promoting tumour cell spreading by interaction with tumour cell-associated MUC1, circulating PNA might also influence metastasis by enhancing the secretion of metastasis-promoting MCP-1 and IL-6 from the vascular endothelium.
| Item Type: | Article |
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| Uncontrolled Keywords: | Endothelium, Vascular, Cells, Cultured, Animals, Mice, Inbred BALB C, Humans, Mice, Neoplasm Metastasis, Cell Adhesion Molecules, Peanut Agglutinin, Inflammation Mediators, Cytokines, Signal Transduction, Female, Mucin-1, Arachis |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 02 Aug 2021 09:11 |
| Last Modified: | 18 Jan 2023 21:34 |
| DOI: | 10.1093/carcin/bgab059 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3131701 |
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