Expression and function of the receptor protein tyrosine phosphatase ζ and its ligand pleiotrophin in human astrocytomas

U Ulbricht, MA Brockmann, A Aigner… - … of Neuropathology & …, 2003 - academic.oup.com
U Ulbricht, MA Brockmann, A Aigner, C Eckerich, S Müller, R Fillbrandt, M Westphal…
Journal of Neuropathology & Experimental Neurology, 2003academic.oup.com
Using subtractive cloning combined with cDNA array analysis, we previously identified the
genes encoding for the protein tyrosine phosphatase ζ/receptor-type protein tyrosine
phosphatase β (PTPζ/RPTPβ) and its ligand pleiotrophin (PTN) as overexpressed in human
glioblastomas compared to normal brain. Both molecules have been implicated in neuronal
migration during central nervous system development, and PTN is known to be involved in
tumor growth and angiogenesis. We confirm overexpression of both molecules at the protein …
Abstract
Using subtractive cloning combined with cDNA array analysis, we previously identified the genes encoding for the protein tyrosine phosphatase ζ/receptor-type protein tyrosine phosphatase β (PTPζ/RPTPβ) and its ligand pleiotrophin (PTN) as overexpressed in human glioblastomas compared to normal brain. Both molecules have been implicated in neuronal migration during central nervous system development, and PTN is known to be involved in tumor growth and angiogenesis. We confirm overexpression of both molecules at the protein level in astrocytic gliomas of different malignancy grades. PTPζ/RPTPβ immunoreactivity was associated with increasing malignancy grade and localized predominantly to the tumor cells. PTN immunoreactivity as determined by ELISA and immunohistochemistry analysis was increased in low-grade astrocytomas compared to normal brain. Further increase in malignant gliomas was marginal, and thus no correlation with malignancy grade or microvessel density was present. However, PTN levels were significantly associated with those of fibroblast growth factor-2, suggesting co-regulation of both factors. Functionally, PTN induced weak chemotactic and strong haptotactic migration of glioblastoma and cerebral microvascular endothelial cells. Haptotaxis of glioblastoma cells towards PTN was specifically inhibited by an anti-PTPζ/RPTPβ antibody. Our findings suggest that upregulated expression of PTN and PTPζ/RPTPβ in human astrocytic tumor cells can create an autocrine loop that is important for glioma cell migration. Although PTN is a secreted growth factor, it appears to exert its mitogenic effects mostly in a matrix-immobilized form, serving as a substrate for migrating tumor cells.
Oxford University Press