title: Peanut agglutinin appearance in the blood circulation after peanut ingestion mimics the action of endogenous galectin-3 to promote metastasis by interaction with cancer-associated MUC1.
abstract: Peanut agglutinin (PNA), which accounts for ~0.15% of the weight of the common peanut, is a carbohydrate-binding protein that binds the oncofoetal Thomsen-Friedenreich (TF) disaccharide (galactoseβ1,3N-acetylgalactosamineα-) that is overexpressed by ~90% of human cancers. Previous studies have shown that PNA is highly resistant to cooking and digestion and rapidly enters the human blood circulation after peanut ingestion. This study investigates the hypothesis that PNA appearance in the circulation after peanut ingestion may mimic the actions of endogenous TF-binding human galectin-3 in metastasis promotion. It shows that PNA at concentrations similar to those found in blood circulation after peanut ingestion increases cancer cell heterotypic adhesion to the blood vascular endothelium and enhances the formation of tumour cell homotypic aggregates, two important steps in the metastasis cascade, and enhances metastasis in a mouse metastasis model. These effects of PNA are shown to result from its interaction with the cancer-associated TF disaccharide on the transmembrane mucin protein MUC1, causing MUC1 cell surface polarization that reveals underlying cell surface adhesion molecules. Thus, PNA appearance in the blood circulation after peanut ingestion mimics the actions of endogenous galectin-3 and promotes cancer cell metastatic spread by interaction with cancer-associated TF/MUC1. As metastasis accounts for the majority of cancer-associated fatality, regular consumption of peanuts by cancer patients would therefore be expected to have an adverse effect on cancer survival.
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK andDepartment of Pharmacology, Shandong University, Shandong 250012, China.
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK andDepartment of Pharmacology, Shandong University, Shandong 250012, China.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Duckworth
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK andDepartment of Pharmacology, Shandong University, Shandong 250012, China.
authors.forename: Weikun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shandong University, Shandong 250012, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK andDepartment of Pharmacology, Shandong University, Shandong 250012, China.
authors.forename: Hannah
authors.initials: H
authors.lastname: Barrow
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK andDepartment of Pharmacology, Shandong University, Shandong 250012, China.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK andDepartment of Pharmacology, Shandong University, Shandong 250012, China.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Rhodes
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK andDepartment of Pharmacology, Shandong University, Shandong 250012, China lgyu@liv.ac.uk.
authors.forename: Lu-Gang
authors.initials: LG
authors.lastname: Yu
mesh_terms: D000818:Animals; D023102:Anoikis / Q000187:drug effects; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018396:Mucin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D019887:Peanut Agglutinin / Q000097:blood / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D037502:Galectin 3; C060192:MUC1 protein, human; D018396:Mucin-1; D019887:Peanut Agglutinin; D034741:RNA, Small Interfering