Neural stem cell‐like gene expression in a mouse ependymoma cell line transformed by human BK polyomavirus

• Published in: Cancer science 2011-01, Vol.102 (1), p.122-129
• Main Authors: Aizawa, Takako, Hasegawa, Koichi, Ohkumo, Tsuyoshi, Haga, Seiichi, Ikeda, Kazuhiko, Yoshikawa, Kazuaki
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biomarkers; BK Virus - pathogenicity; Cell Line, Tumor; Cell Transformation, Neoplastic; Ependymoma - metabolism; Ependymoma - pathology; Glial Fibrillary Acidic Protein; Homeodomain Proteins - analysis; Homeodomain Proteins - genetics; Humans; Immunohistochemistry; Indexing in process; Medical sciences; Melanoma-Specific Antigens - genetics; Mice; Mice, Inbred BALB C; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - genetics; Neural Stem Cells - metabolism; Neurology; Nuclear Proteins - analysis; Nuclear Proteins - genetics; Polycomb Repressive Complex 1; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins - genetics; Repressor Proteins - analysis; Repressor Proteins - genetics; RNA, Messenger - analysis; Transcription Factors - analysis; Transcription Factors - genetics; Tumors; Tumors of the nervous system. Phacomatoses
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2010.01775.x

Ependymomas often show characteristics similar to those of neural stem cells in vivo and in vitro. However, few ependymoma cell lines that exhibit neural stem cell‐like properties have been reported. In this study, we have characterized a novel cell line, designated Vn19, established from ependymoma that arose in mice inoculated intracerebrally with human BK polyomavirus. Transplanted Vn19 cells in nude mice ubiquitously expressed viral large T antigen in the nucleus and coexpressed neuronal and glial marker proteins in vivo. Remarkably, individual Vn19 cells in dispersed cultures simultaneously expressed marker proteins of neural stem cells (nestin, Bmi1, CD133), neurons (βIII tubulin, neurofilament‐M) and glial cells (glial fibrillary acidic protein, A2B5, S100β, O4). Ubiquitous and homogenous expression of these multilineage marker proteins was also observed in cloned Vn19 cells. The Vn19 cells formed neurosphere‐like aggregates when cultured in the presence of growth factors. Quantitative RT‐PCR analysis revealed that expression of mRNA for nestin, neurofilament‐H and glial fibrillary acidic protein significantly increased in Vn19 cells cultured under growth factor‐deprived conditions. Among MAGE (melanoma antigen) family genes, MAGE‐A (A1‐8), MAGE‐B (B1‐3), MAGE‐D1, MAGE‐E1, MAGE‐G1 (necdin‐like 2) and MAGE‐H1 were expressed in the Vn19 cells, in which neither necdin nor MAGEL2 was detectable. These results suggest that this murine ependymoma cell line recapitulates the gene expression profile in ependymal cells undergoing malignant transformation. (Cancer Sci 2011; 102: 122–129)