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


RESULTS
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 (Galbeta1,3GalNAcalpha-, 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).


CONCLUSIONS
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.
Zhao
Qicheng
Q
Gastroenterology Research Unit, School of Clinical Sciences, Centre for Glycobiology, University of Liverpool, Liverpool L69 3GE, UK.
Barclay
Monica
M
Hilkens
John
J
Guo
Xiuli
X
Barrow
Hannah
H
Rhodes
Jonathan M
JM
Yu
Lu-Gang
LG
D023102:Anoikis; D015820:Cadherins / Q000378:metabolism; D002459:Cell Fusion; D045744:Cell Line, Tumor; D037502:Galectin 3 / Q000097:blood*; D006801:Humans; D018396:Mucin-1 / Q000097:blood*
D015820:Cadherins; D037502:Galectin 3; C060192:MUC1 protein, human; D018396:Mucin-1