Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis

Molecular Cancer

Research

John Hilkens¹  Qicheng Zhao²  Monica Barclay²  Hannah Barrow²  Jonathan M Rhodes²  Lu-Gang Yu²  Xiuli Guo² 

[1] Division of Molecular Genetics, the Netherlands Cancer Institute, 1066, Amsterdam, CX, Netherlands;Gastroenterology Research Unit, School of Clinical Sciences, Centre for Glycobiology, University of Liverpool, L69 3GE, Liverpool, UK;

关键词: HT29 Cell;    Circulate Tumour Cell;    Cell Aggregation;    Cell Aggregate;    Disseminate Tumour Cell;   

DOI  :  10.1186/1476-4598-9-154

 received in 2010-02-01, accepted in 2010-06-18,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundFormation of tumour cell aggregation/emboli prolongs the survival of circulating tumour cells in the circulation, enhances their physical trapping in the micro-vasculature and thus increases metastatic spread of the cancer cells to remote sites.ResultsIt shows here that the presence of the galactoside-binding galectin-3, whose concentration is markedly increased in the blood circulation of cancer patients, increases cancer cell homotypic aggregation under anchorage-independent conditions by interaction with the oncofetal Thomsen-Friedenreich carbohydrate (Galβ1,3GalNAcα-, TF) antigen on the cancer-associated transmembrane mucin protein MUC1. The galectin-3-MUC1 interaction induces MUC1 cell surface polarization and exposure of the cell surface adhesion molecules including E-cadherin. The enhanced cancer cell homotypic aggregation by galectin-MUC1 interaction increases the survival of the tumour cells under anchorage-independent conditions by allowing them to avoid initiation of anoikis (suspension-induced apoptosis).ConclusionThese results suggest that the interaction between free circulating galectin-3 and cancer-associated MUC1 promotes embolus formation and survival of disseminating tumour cells in the circulation. This provides new information into our understanding of the molecular mechanisms of cancer cell haematogenous dissemination and suggests that targeting the interaction of circulating galectin-3 with MUC1 in the circulation may represent an effective therapeutic approach for preventing metastasis.

【 授权许可】

Unknown   
© Zhao et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.