Increased invasive capacity of connexin43-overexpressing malignant glioma cells

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Publication Type Journal Article
School or College School of Medicine
Department Neurosurgery
Creator Couldwell, William T.
Other Author Zhang, Wei; Nwagwu, Chiedozie; Le, Duc Minh; Yong, V. Wee; Song, Hua
Title Increased invasive capacity of connexin43-overexpressing malignant glioma cells
Date 2003-12
Description Object. Malignant glioma cells, similar to astrocytes, express connexin43 (Cx43) universally but at widely varied levels. Data from previous studies have demonstrated that malignant glioma cells form functional gap junction channels among themselves as well as with astrocytes and that such a communication has the potential to modulate the phenotypic characteristics of astrocytes. Recently, gap junctions have been demonstrated to play a role in the invasive phenotype of malignant gliomas. In this study, the authors have further investigated the motility and invasion ability of Cx43-overexpressing and Cx43-deficient malignant glioma cells. Methods. Using a standard invasion system of a Matrigel transwell invasion chamber, the authors found that the number of Cx43-transfected C6 glioma cells (C6-Cx43 cells) migrating through the Matrigel-coated membrane was similar to that of mock-transfected control cells (C6-mock cells) during the first 24 hours, but increased significantly thereafter. When these cells were cocultured with astrocytes, the number of invading C6-Cx43 cells was more than threefold greater than the number of invading C6-mock cells. Results of an in vitro cell motility assay also demonstrated that C6-Cx43 cells were more motile and scatter-active than C6-mock cells. Furthermore, zymographic analysis of MMPs, an important determinant in glioma invasion, demonstrated that the amounts of MMP-2 and MMP-9 in culture medium collected from C6-Cx43 cells were orders of magnitude higher than those from C6-mock cells. In addition, BB-94, a synthetic MMP inhibitor, significantly inhibited C6-Cx43 cell invasion. Conclusions. The overexpression of gap junction proteins in glioma cells and the intercellular communication between tumor and nontumor glia cells may play important roles in the facilitation of glioma cell invasion.
Type Text
Publisher American Association of Neurological Surgeons (AANS)
Journal Title Journal of Neurosurgery
Volume 99
Issue 6
First Page 1039
Last Page 1046
DOI 10.3171/jns.2003.99.6.1039
citatation_issn 0022-3085
Language eng
Bibliographic Citation Zhang, W., Nwagwu, C., Le, D. M., Yong, V. W., Song, H., & Couldwell, W. T. (2003). Increased invasive capacity of connexin43-overexpressing malignant glioma cells. Journal of Neurosurgery, 99(6), 1039-46.
Rights Management (c) American Association of Neurological Surgeons
Format Medium application/pdf
Format Extent 432,489 bytes
Identifier ir-main,12608
ARK ark:/87278/s69z9pck
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2021-05-06
ID 705582
Reference URL