Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity

Jia Jean Yiin, Bo Hu*, Michael J. Jarzynka, Haizhong Feng, Kui Wei Liu, Jane Y. Wu, Hsin I. Ma, Shi Yuan Cheng

*Corresponding author for this work

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Slit2, a chemorepulsive factor, controls cell migration of neuronal and glial cells during development and inhibits chemotaxic migration of various types of cells in vitro. However, the role of Slit2 in vitro remains controversial, and the biological significance of Slit2 expression in cancer cell invasion in vivo has not yet been determined. In the present study, we characterized the effects of Slit2 expression on the migration and invasion of invasive glioma cells in vitro and in vivo. By reverse transcriptase polymerase chain reaction (PCR) analyses, Slit2 was found to be expressed at lower levels in primary glioma specimens and invasive glioma cells compared with normal human brain cells and astrocytes. Ectopic expression of Slit2 or treatment with recombinant Slit2 on glioma cells attenuates cell migration and invasion through inhibition of Cdc42 activity in vitro. Cellular depletion of Robo1, a cognate receptor for Slit2, prevented Slit2 inhibition of Cdc42 activity and glioma cell migration. In vivo, expression of Slit2 by invasive SNB19 glioma cells markedly inhibited glioma cell infiltration into the brain of mice. Moreover, impediment of glioma cell invasion by Slit2 did not affect the expression of N-cadherin and β-catenin in glioma cells. These results provide the first evidence demonstrating that Slit2-Robo1 inhibits glioma invasion through attenuating Cdc42 activity in vitro and in the brain. Understanding the mechanisms of Slit2-Robo1 inhibition of glioma cell invasion will foster new treatments for malignant gliomas.

Original languageEnglish (US)
Pages (from-to)779-789
Number of pages11
JournalNeuro-oncology
Volume11
Issue number6
DOIs
StatePublished - Jan 1 2009

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Glioma
Brain
Cell Movement
Catenins
Cadherins
Reverse Transcriptase Polymerase Chain Reaction
Neuroglia
Astrocytes
In Vitro Techniques

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Yiin, Jia Jean ; Hu, Bo ; Jarzynka, Michael J. ; Feng, Haizhong ; Liu, Kui Wei ; Wu, Jane Y. ; Ma, Hsin I. ; Cheng, Shi Yuan. / Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity. In: Neuro-oncology. 2009 ; Vol. 11, No. 6. pp. 779-789.
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abstract = "Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Slit2, a chemorepulsive factor, controls cell migration of neuronal and glial cells during development and inhibits chemotaxic migration of various types of cells in vitro. However, the role of Slit2 in vitro remains controversial, and the biological significance of Slit2 expression in cancer cell invasion in vivo has not yet been determined. In the present study, we characterized the effects of Slit2 expression on the migration and invasion of invasive glioma cells in vitro and in vivo. By reverse transcriptase polymerase chain reaction (PCR) analyses, Slit2 was found to be expressed at lower levels in primary glioma specimens and invasive glioma cells compared with normal human brain cells and astrocytes. Ectopic expression of Slit2 or treatment with recombinant Slit2 on glioma cells attenuates cell migration and invasion through inhibition of Cdc42 activity in vitro. Cellular depletion of Robo1, a cognate receptor for Slit2, prevented Slit2 inhibition of Cdc42 activity and glioma cell migration. In vivo, expression of Slit2 by invasive SNB19 glioma cells markedly inhibited glioma cell infiltration into the brain of mice. Moreover, impediment of glioma cell invasion by Slit2 did not affect the expression of N-cadherin and β-catenin in glioma cells. These results provide the first evidence demonstrating that Slit2-Robo1 inhibits glioma invasion through attenuating Cdc42 activity in vitro and in the brain. Understanding the mechanisms of Slit2-Robo1 inhibition of glioma cell invasion will foster new treatments for malignant gliomas.",
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Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity. / Yiin, Jia Jean; Hu, Bo; Jarzynka, Michael J.; Feng, Haizhong; Liu, Kui Wei; Wu, Jane Y.; Ma, Hsin I.; Cheng, Shi Yuan.

In: Neuro-oncology, Vol. 11, No. 6, 01.01.2009, p. 779-789.

Research output: Contribution to journalArticle

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T1 - Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity

AU - Yiin, Jia Jean

AU - Hu, Bo

AU - Jarzynka, Michael J.

AU - Feng, Haizhong

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AU - Cheng, Shi Yuan

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