Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma

Pećina‑Šlaus,Nives; Kafka,Anja; Varošanec,Ana Maria; Marković,Leon; Krsnik,Željka; Njirić,Niko; Mrak,Goran

doi:10.3892/mmr.2016.5061

Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma

Authors:
- Nives Pećina‑Šlaus
- Anja Kafka
- Ana Maria Varošanec
- Leon Marković
- Željka Krsnik
- Niko Njirić
- Goran Mrak
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Affiliations: Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb HR‑10000, Croatia, Department of Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb HR‑10000, Croatia, Department of Neurosurgery, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb HR‑10000, Croatia
Published online on: March 28, 2016 https://doi.org/10.3892/mmr.2016.5061
Pages: 4245-4251
Copyright: © Pećina‑Šlaus et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an increased expression level of SFRP3 was identified in the high grade astrocytomas when compared with those of a low grade. This may suggest that SFRP3 acts as an agonist of Wnt signaling and promotes invasive behavior.

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