Increased expression of midkine during the progression of human astrocytomas.

Midkine (MK), a member of a new family of neurotrophic and angiogenic growth factors whose expression is developmentally regulated, is produced in fetal astrocytes. Malignant astrocytomas, one of the most neovascularized tumors, are derived from astrocytes. There has been no investigation of the expression of MK in human astrocytic tumors. To determine if increased levels of MK expression correlate with the progression of human astrocytomas, we examined surgical specimens of astrocytic tumors of various grades using Northern and Western blotting. MK mRNA and protein expression levels were higher in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas) than in low-grade astrocytomas. As shown by in situ hybridization, MK mRNA expression was intense in a majority of glioblastoma cells but was weak in a small number of low-grade astrocytoma cells. These findings suggest that MK expression correlates with the malignant progression of astrocytomas. The aberrant MK expression in high-grade astrocytomas may underlie their rapid growth and well-vascularized features.