Sialyltransferase Inhibitor Ac53FaxNeu5Ac Reverts the Malignant Phenotype of Pancreatic Cancer Cells, and Reduces Tumor Volume and Favors T-Cell Infiltrates in Mice

Abstract

An increase of sialic acid in the cancer cells’ surface is a hallmark of tumours, including pancreatic cancer, and it has been related to tumour malignancy and immune suppression. In this work, we have assessed for the first time the potential of the sialyltransferase inhibitor, Ac53FaxNeu5Ac, to reduce tumor sialylation in pancreatic cancer and to revert its malignant phenotype. We have shown that Ac53FaxNeu5Ac treatment on human pancreatic cancer cells decreased their sialic acid, reduced their E-selectin adhesion—the prior step to tumour extravasation—and their migration and invasion capabilities. In addition, subcutaneous pancreatic tumours generated on immunocompetent mice that were treated with Ac53FaxNeu5Ac showed a reduced growth and increased tumour infiltrating lymphocytes. These results show that the targeting of tumour sialoglycans in pancreatic cancer reverts its malignant phenotype and favours anti-tumour immune surveillance, which opens the way to use sialyltransferase inhibitors as a novel therapeutic strategy against this dismal disease