Jagged1 contributes to the drug resistance of Jurkat cells in contact with human umbilical cord-derived mesenchymal stem cells

Abstract

Notch signaling, which is driven by the Notch1 receptor, plays an essential role in the pathogenesis and stroma-mediated drug resistance of T-cell acute lymphoblastic leukemia (T-ALL). However, little is known about the roles of Notch ligands in the survival or drug resistance of T-ALL cells. In the present study, isolated mesenchymal stem cells (MSCs) from human umbilical cord (hUC) samples, termed hUC-MSCs, were used as stromal cells for the Jurkat T-ALL cell line. The role of the Notch ligand, Jagged1, was assessed in the survival of Jurkat T-ALL cells using this co-culture system. hUC-MSCs and Jurkat cells were observed to express Jagged1. Furthermore, co-culture with hUC-MSCs led to a significant upregulation of Jagged1 and a more significant overexpression of its receptor, Notch1, in the Jurkat cells, indicating that the receptor and ligand pair may play a role in the reciprocal or autonomous activation of the Notch pathway. In addition, a higher level of CD28 expression was observed in the Jurkat cells that were co-cultured with hUC-MSCs. Blocking Jagged1 expression using neutralizing antibodies restored drug-induced apoptosis in the Jurkat cells that were co-cultured with hUC-MSCs, and also increased the drug sensitivity of the Jurkat cells that were cultured alone. By contrast, direct incubation with exogenously recombinant Jagged1 produced the same protective effects in Jurkat cells as those induced by hUC-MSCs. These results indicate a significant role for Jagged1 in hUC-MSC-induced survival and the self-maintenance of the Jurkat T-ALL cell line, making it a potential target for the treatment of human T-ALL.