title: Native Oligodendrocytes in Astrocytomas Might Inhibit Tumor Proliferation by WIF1 Expression.
abstract: Malignant astrocytoma remains incurable and rapidly fatal despite multimodal therapy. In particular, accelerated tumor cell heterogeneity often overcomes therapeutic effects of molecular protein targeting. This study aimed at identifying a gene with therapeutic potential that was consistently downregulated with astrocytoma progression. Analysis of the "Rembrandt" gene expression data revealed Wnt inhibitory factor 1 (WIF1) gene as the most promising candidate with tumor suppressor function. Consequently, 288 randomly selected tissue regions of astrocytoma specimens were investigated immunohistochemically with the aid of image analysis. This in situ approach identified tumor areas with numerous single cells strongly expressing Wif-1. In diffuse and anaplastic astrocytoma, the proliferation index was independent of the generally weak Wif-1 expression in tumor cells but was significantly correlated with the density of Wif-1-expressing single cells, subsequently characterized as native and non-neoplastic oligodendrocytes. Because these cells may contribute to inhibition of tumor cell proliferation by paracrine signaling, the endogenous protein Wif-1 may represent a promising therapeutic agent with expected minimal side effects. Moreover, we suggest that immunohistochemistry for Wif might be useful for discriminating between astrocytic tumors and reactive changes.
authors.affiliation: Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Asslaber
authors.affiliation: Department of Pathology, Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schauer
authors.affiliation: Department of Pathology, Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Gogg-Kamerer
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Bernhart
authors.affiliation: Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Quehenberger
authors.affiliation: Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D009837:Oligodendroglioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D012097:Repressor Proteins; C485569:WIF1 protein, human
keywords: Astrocytoma; Diagnosis; Glioblastoma; Oligodendrocytes; Proliferation; Therapy; WIF1