Reduction of CD200 expression in glioma cells enhances microglia activation and tumor growth

Chih Yen Wang, Yun Ti Hsieh, Kuan Min Fang, Chung Shi Yang, Shun Fen Tzeng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

CD200, a type I transmembrane glycoprotein, can interact with its receptor CD200R, which plays an inhibitory role in the activation of microglia—the resident macrophages of the central nervous system. In this study, the rat C6 glioma cell line (C6-1) that was previously characterized with high in vivo tumorigenicity was found to generate CD200 mRNA abundantly. However, CD200 expression was barely detected in another C6 glioma cell clone (C6-2) that was previously found to display low tumorigenic behavior. The results from CD200 immunohistochemistry on human glioma tissue array also showed that tumor cells in Grade I–II astrocytoma expressed a lower level of CD200 immunoreactivity than those detected in Grade III–IV glioblastoma multiforme. C6-1 transfectants with stable downregulation of CD200 gene expression using lentivirus knockdown approach were generated (C6-KD). Microglia and iNOS + cells were increased when microglia were co-cultured with C6-KD cells. The colony formation of C6-KD was also augmented when those cells were co-cultured with microglia. Yet, increased colony formation of C6-KD transfectants in the co-culture with microglia was effectively suppressed by interleukin (IL)-4 and IL-10. The in vivo results indicated that the tumor formation of C6-1 cells in rat brain was promoted after CD200 gene knockdown. Moreover, CD11b + activated microglia and iNOS + microglia were highly accumulated in the tumor site formed by C6-KD. In conclusion, our findings demonstrate that the downregulation of CD200 expression in CD200-rich glioma cells could foster the formation of an activated microglia–associated tumor microenvironment, leading to glioma progression.

Original languageEnglish
Pages (from-to)1460-1471
Number of pages12
JournalJournal of Neuroscience Research
Volume94
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1

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Microglia
Glioma
Growth
Neoplasms
Down-Regulation
Gene Knockdown Techniques
Lentivirus
Tumor Microenvironment
Astrocytoma
Glioblastoma
Coculture Techniques
Interleukin-4
Interleukin-10
Glycoproteins
Central Nervous System
Clone Cells
Immunohistochemistry
Macrophages
Gene Expression
Cell Line

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

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title = "Reduction of CD200 expression in glioma cells enhances microglia activation and tumor growth",
abstract = "CD200, a type I transmembrane glycoprotein, can interact with its receptor CD200R, which plays an inhibitory role in the activation of microglia—the resident macrophages of the central nervous system. In this study, the rat C6 glioma cell line (C6-1) that was previously characterized with high in vivo tumorigenicity was found to generate CD200 mRNA abundantly. However, CD200 expression was barely detected in another C6 glioma cell clone (C6-2) that was previously found to display low tumorigenic behavior. The results from CD200 immunohistochemistry on human glioma tissue array also showed that tumor cells in Grade I–II astrocytoma expressed a lower level of CD200 immunoreactivity than those detected in Grade III–IV glioblastoma multiforme. C6-1 transfectants with stable downregulation of CD200 gene expression using lentivirus knockdown approach were generated (C6-KD). Microglia and iNOS + cells were increased when microglia were co-cultured with C6-KD cells. The colony formation of C6-KD was also augmented when those cells were co-cultured with microglia. Yet, increased colony formation of C6-KD transfectants in the co-culture with microglia was effectively suppressed by interleukin (IL)-4 and IL-10. The in vivo results indicated that the tumor formation of C6-1 cells in rat brain was promoted after CD200 gene knockdown. Moreover, CD11b + activated microglia and iNOS + microglia were highly accumulated in the tumor site formed by C6-KD. In conclusion, our findings demonstrate that the downregulation of CD200 expression in CD200-rich glioma cells could foster the formation of an activated microglia–associated tumor microenvironment, leading to glioma progression.",
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Reduction of CD200 expression in glioma cells enhances microglia activation and tumor growth. / Wang, Chih Yen; Hsieh, Yun Ti; Fang, Kuan Min; Yang, Chung Shi; Tzeng, Shun Fen.

In: Journal of Neuroscience Research, Vol. 94, No. 12, 01.12.2016, p. 1460-1471.

Research output: Contribution to journalArticle

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T1 - Reduction of CD200 expression in glioma cells enhances microglia activation and tumor growth

AU - Wang, Chih Yen

AU - Hsieh, Yun Ti

AU - Fang, Kuan Min

AU - Yang, Chung Shi

AU - Tzeng, Shun Fen

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