Tumour-associated Mucin1 correlates with the procoagulant properties of cancer cells of epithelial origin

Abstract

Background

Cancer-associated thrombosis (CAT) is caused, at least in part, by procoagulant factors produced by the tumour itself. Although MUC1 is an established biomarker for the diagnosis, immunotherapy, and prognosis of cancer, it is unclear whether it contributes to the procoagulant phenotype of cancer cells.

Methods

MUC1 knockdown breast cancer MCF-7 cells were used to investigate the influence of overexpression of MUC1 on procoagulant parameters. In addition, the effect of treating normal human epithelial cells with extracellular vesicles from several human breast and pancreatic cancer cell lines, which overexpress MUC1, was determined. The impact of a pharmacological anti-MUC1 antibody on cancer cells was also analysed.

Results

The level of a range of procoagulant proteins was observed to correlate with the MUC1 level of human breast and pancreatic cancer cell lines. MUC1 downregulation in MCF-7 cells led to a reduction in the procoagulant parameters particularly thrombin activity. The levels of selected tumorigenic markers, procoagulant proteins and miRNAs associated with tumorigenicity and thromboembolism were also modulated by treatment of normal cells with tumour cell derived extracellular vesicles in correlation with that of the extracellular vesicles donor cells. Moreover, the procoagulant properties were also reduced by an anti-MUC1 antibody in these cancer cells.

Conclusions

A range of procoagulant proteins found in human breast and pancreatic cancer cells were shown to exhibit a positive correlation with the level of MUC1 and thereby potentially contribute to the pathogenesis of CAT. The reduction of the procoagulant activity by MUC1 antibody could be an additional beneficial effect of its therapeutic efficacy. These findings also suggest that the level of tumour associated MUC1 could be of use as a risk factor for CAT.