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: Qicheng Zhao, Carrie A Duckworth, Weikun Wang, Xiuli Guo, Hannah Barrow, D Mark Pritchard, Jonathan M Rhodes, Lu-Gang Yu
• Journal: Carcinogenesis (Carcinogenesis) Vol. 35 Issue 12 Pg. 2815-21 (Dec 2014) ISSN: 1460-2180 [Electronic] England
• PMID: 25326505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Galectin 3
• MUC1 protein, human
• Mucin-1
• Peanut Agglutinin
• RNA, Small Interfering

Topics

• Animals
• Anoikis (drug effects)
• Apoptosis
• Blotting, Western
• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Colonic Neoplasms (drug therapy, metabolism, secondary)
• Endothelium, Vascular (drug effects, metabolism, pathology)
• Female
• Galectin 3 (metabolism)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mucin-1 (chemistry, genetics, metabolism)
• Neoplasm Metastasis
• Peanut Agglutinin (blood, pharmacology)
• RNA, Small Interfering (genetics)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays