We showed that the knockdown of MDK expression by siRNA led to a marked and significant decrease in neuroblastoma (IGR-N91 and SH-SY5Y) cell proliferation in vitro.
These results indicate that neuroblastoma cells are highly dependent on midkine and that a midkine-targeted therapy could exert a significant effect in these cells.
Our findings establish a critical role for the midkine-Notch2 signaling axis in neuroblastoma tumorigenesis, which implicates new strategies to treat neuroblastoma.
We previously reported that MK mRNA expression is elevated in neuroblastoma specimens at all stages, whereas pleiotrophin, the other member of the MK family, is expressed at high levels in favourable neuroblastomas.
A conditionally replicative Ad in which the expression of E1 is controlled by the MK promoter achieved good levels of viral replication in NB or ES and induced remarkable tumor cell killing.