Midkine is highly expressed in various
cancers, including
neuroblastoma, one of the most malignant paediatric solid tumours known. Also, it has been shown to be useful as a tumour marker, a prognosis factor and a target of molecular
therapy. Several molecular tools (e.g.
siRNA,
antibodies and
RNA aptamer) have been used to establish a
midkine-targeted
therapy. The involvement of
midkine in tumourigenesis has been demonstrated in vivo in a mouse
neuroblastoma model, where targeting it with an
RNA aptamer was shown to be an effective treatment for xenografted tumours. Chemoresistance is one of the notable phenotypes regulated by
midkine in various
cancer cell types. In pancreatic tumours and
glioma cells,
midkine is expressed in chemoresistant cells and is involved in the survival of these cells in the presence of anticancer drugs. In contrast to these tumours,
midkine was found to be expressed in every
neuroblastoma cell line tested and the knockdown of
midkine alone was sufficient to suppress their growth. 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. However, to achieve a
midkine-targeted
therapy for high-risk
neuroblastoma patients, the further refinement of the
RNA aptamer or antibody as tools and the elucidation of
midkine signalling are immediate issues that need to be resolved. Regarding the latter, although it has been shown that Notch2 functions as a receptor in
neuroblastoma cells, it is likely that other receptors (e.g.
anaplastic lymphoma kinase) are also involved in
midkine signalling.
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