%0 Journal Article
%T Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis
%A Qicheng Zhao
%A Monica Barclay
%A John Hilkens
%A Xiuli Guo
%A Hannah Barrow
%A Jonathan M Rhodes
%A Lu-Gang Yu
%J Molecular Cancer
%D 2010
%I BioMed Central
%R 10.1186/1476-4598-9-154
%X It 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 (Gal¦Â1,3GalNAc¦Á-, 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).These 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.Formation of tumour cell aggregation/emboli in the circulation prolongs the survival of tumour cells and allows their physical trapping in the micro-vasculature and contributes to cancer cell hematogenous dissemination [1,2]. The formation of tumour emboli is heavily regulated by the expression, availability and activity of the cell surface adhesion molecules.Galectin-3 is a multi-functional galactoside-binding protein that is expressed by many types of human cells. It is found inside and outside of the cells as well as in the circulation. Intracellular galectin-3 is an apoptosis inhibitor [3] and mRNA splicing promoter [4] whilst cell surface-associated extracellular galectin-3 acts as an adhesion molecule in cell-ce
%U http://www.molecular-cancer.com/content/9/1/154