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Correlation
of N-cadherin expression in high grade gliomas with tissue invasion
Kenichiro
Asano, Christopher D. Duntsch, Qihong Zhou, James D. Weimar, Dwight Bordelon,
Jon H. Robertson, Tayebeh Pourmotabbed
Department
of Neurosurgery, The University of Tennessee Health Science Center, Memphis, TN,
USA [K.A., C.D.D., Q.Z., J.D.W., D.B., J.H.R.]; Department of Molecular
Sciences, The University of Tennessee Health Science Center, Memphis, TN, USA
[T.P.]; Department of Neurosurgery, Hirosaki University School of Medicine,
Hirosaki, Japan [K.A.]. Correspondence to: [K.A.], Department of Neurosurgery, Hirosaki
University School of Medicine, Zaifu-cho 5, Hirosaki City, Aomori Prefecture,
036-8562, Japan; Tel.: 81-172-39-5115; Fax: 81-172-39-5116; E-mail: asanoken@cc.hirosaki-u.ac.jp
Cadherins
are Ca2+-dependent cell adhesion molecules that play an important
role in tissue construction and morphogenesis in multicellular organisms.
Over the last few years, reports have emerged in the literature describing the
involvement of cadherins in tumor invasion and metastasis.
Cadherins typically demonstrate up and down-regulation according to the
biological needs of the tissue.
Additionally, up-regulation of N-cadherin is thought to be important for tumor
formation in early stages of tumor development.
We studied N-cadherin in surgical specimens of patients with primary
glioblastoma by microarray analysis and found that N-cadherin mRNA expression is
up-regulated compared to normal brain.
To study the effects of N-cadherin expression on invasion and metastasis in
vitro and in
vivo, we
overexpressed N-cadherin in the rat C6 glioma cell line which normally has low
levels of N-cadherin.
We found that up-regulation of N-cadherin resulted in a slight decreased
adhesion to type IV collagen, fibronectin, and laminin, but statistically
significant decreased adhesion to type I collagen.
Furthermore, increased expression of N-cadherin correlated with a dramatic
decrease in invasive behavior in extracellular matrix invasion assays.
We then proceeded to study these cell lines in
vivo in a rat
intracranial glioma model, and found that N-cadherin expression inversely
correlated with invasion into surrounding tissues, irregular margins, and
extracranial invasion.
In summary, these data collectively demonstrate that N-cadherin levels are
important in the malignant behavior of gliomas, and may serve as a prognostic
indicator for patients with high-grade gliomas.
Keywords: cell adhesion, glioblastoma,
high-grade glioma, invasion, N-cadherin
Copyright
© 2004 Kluwer
Academic Publishers. All rights reserved
Source: http://ipsapp009.kluweronline.com/IPS/content/ext/x/J/5042/I/123/A/3/abstract.htm
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