Communication between malignant glioma cells and vascular endothelial cells through gap junctions

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Publication Type Journal Article
School or College School of Medicine
Department Neurosurgery
Creator Couldwell, William T.
Other Author Zhang, Wei; DeMattia, Joseph A.; Song, Hua
Title Communication between malignant glioma cells and vascular endothelial cells through gap junctions
Date 2003-01-01
Description Object. Extensive invasion and angiogenesis are hallmark features of malignant gliomas. Communication between malignant glioma cells and surrounding astrocytes occurs, resulting in transformation of the astrocytic phenotype. In the present study, the authors examined whether malignant glioma cells and vascular endothelial cells (VECs) communicate through the formation of gap junctions and whether this communication influences angiogenesis. Methods. Connexin43 (Cx43), a gap junction protein expressed in glioma cells, was identified in human umbilical VECs (HUVECs). Immunocytochemical staining for Cx43 demonstrated immunoreactive plaques at areas of cell-cell contact among HUVECs as well as between HUVECs and Cx43-expressing malignant glioma cells. Dye transfer, performed using the gap junction-permeable dye dicarboxy-dichlorofluorescein diacetate (CDCF), among these cocultures indicated that these were functional communications. Calcium signaling also occurred from malignant glioma cells to HUVECs. Tube formation by HUVECs cocultured with Cx43-transfected T98G malignant glioma cells (T98G-Cx43 cells) or with U87MG malignant glioma cells, which naturally express Cx43, was significantly increased compared with tube formation by HUVECs alone. The difference in tube formation by HUVECs cocultured with empty vector-transfected T98G glioma cells (T98G-mock cells) or with Cx43-deficient U373MG malignant glioma cells and tube formation by HUVECs alone was not statistically significant. Furthermore, the concentration of vascular endothelial growth factor (VEGF), an angiogenic factor important for the induction of angiogenesis and blood vessel formation, was significantly higher in medium harvested from cultures of T98G-Cx43 cells than in that harvested from cultures of control T98G-mock cells. Human malignant glioma U87MG cells also secreted increased concentrations of VEGF as compared with HUVECs alone. Nevertheless, there was no statistically significant difference in tube formation by HUVECs cultured in medium conditioned by either Cx43-expressing or Cx43-deficient glioma cells, suggesting that the direct gap junction communication between glioma cells and HUVECs may play a much more significant role than the increased VEGF secretion in vascular tube formation in this assay. Conclusions. These results indicate that functional gap junction formation between human malignant glioma cells and VECs occurs. This communication appears to influence tumor angiogenesis. Targeting gap junction signaling may offer a potential mechanism for therapy in patients with these tumors.
Type Text
Publisher American Association of Neurological Surgeons (AANS)
Volume 98
Issue 4
First Page 846
Last Page 853
Language eng
Bibliographic Citation Zhang, W., DeMattia, J. A., Song, H., & Couldwell, W. T. (2003). Communication between malignant glioma cells and vascular endothelial cells through gap junctions. Journal of Neurosurgery, 98(4), 846-53.
Rights Management (c) American Association of Neurological Surgeons
Format Medium application/pdf
Format Extent 354,051 bytes
Identifier ir-main,12601
ARK ark:/87278/s6f19h1z
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 704558
Reference URL https://collections.lib.utah.edu/ark:/87278/s6f19h1z
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