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

Zhang, Wei; DeMattia, Joseph A.; Song, Hua; Couldwell, William T.

doi:10.3171/jns.2003.98.4.0846

Cited by 58 publications

(47 citation statements)

References 16 publications

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“…Substantial evidence from various models implicates cell-cell communication in the ability of tumor cells to invade and metastasize. Intercellular communication between glioma tumor cells and astrocytes or endothelial cells was shown to increase tumor invasion and to increase vascular endothelial growth factor secretion and vascular tube formation, respectively (9,15,16). In prostate cancer, a direct correlation between increased connexin 26 expression levels and cancer progression was observed (17).…”

Section: Discussionmentioning

confidence: 95%

Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo

Challita-Eid¹,

Morrison²,

Etessami³

et al. 2007

Cancer Research

110

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Six-transmembrane epithelial antigen of the prostate-1 (STEAP-1) is a novel cell surface protein highly expressed in primary prostate cancer, with restricted expression in normal tissues. In this report, we show STEAP-1 expression in prostate metastases to lymph node and bone and in the majority of human lung and bladder carcinomas. We identify STEAP-1 function in mediating the transfer of small molecules between adjacent cells in culture, indicating its potential role in tumor cell intercellular communication. The successful generation of two monoclonal antibodies (mAb) that bind to cell surface STEAP-1 epitopes provided the tools to study STEAP-1 susceptibility to naked antibody therapy. Both mAbs inhibited STEAP-1-induced intercellular communication in a dosedependent manner. Furthermore, both mAbs significantly inhibited tumor growth in mouse models using patientderived LAPC-9 prostate cancer xenografts and established UM-UC-3 bladder tumors. These studies validate STEAP-1 as an attractive target for antibody therapy in multiple solid tumors and provide a putative mechanism for mAb-induced tumor growth inhibition. [Cancer Res 2007;67(12):5798-805]

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Section: Discussionmentioning

confidence: 95%

Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo

Challita-Eid¹,

Morrison²,

Etessami³

et al. 2007

Cancer Research

110

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“…On the other hand, connexins can enhance the invasive potential of cancer cells in a GJIC-dependent as well as GJICindependent manner [13][14][15]. While GJIC between cancer and endothelial cells was shown to facilitate cancer cell penetration of the endothelial layer [16,17], a GJIC-independent function of Cx43 in brain tumour invasion was reported [14]. These observations suggest the stage-specific function of connexins in the process of cancer development [15].…”

Section: Introductionmentioning

confidence: 88%

DU-145 prostate carcinoma cells that selectively transmigrate narrow obstacles express elevated levels of Cx43

Szpak

Wybieralska

Niedzialkowska

et al. 2011

Cellular and Molecular Biology Letters

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The formation of aqueous intercellular channels mediating gap junctional intercellular coupling (GJIC) is a canonical function of connexins (Cx). In contrast, mechanisms of GJIC-independent involvement of connexins in cancer formation and metastasis remain a matter of debate. Because of the role of Cx43 in the determination of carcinoma cell invasive potential, we addressed the problem of the possible Cx43 involvement in early prostate cancer invasion. For this purpose, we analysed Cx43-positive DU-145 cell subsets established from the progenies of the cells most readily transmigrating microporous membranes. These progenies displayed motile activity similar to the control DU-145 cells but were characterized by elevated Cx43 expression levels and GJIC intensity. Thus, apparent links exist between Cx43 expression and transmigration potential of DU-145 cells. Moreover, Cx43 expression profiles in the analysed DU-145 subsets were not affected by intercellular contacts and chemical inhibition of GJIC during the transmigration. Our observations indicate that neither cell motility nor GJIC determines the transmigration efficiency of DU-145 cells. However, we postulate that selective transmigration of prostate cancer cells expressing elevated levels of Cx43 expression may be crucial for the “leading front” formation during cancer invasion.

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“…33 To confirm Connexin43 expression on the U87mg cell line in our hands, we labeled U87mg cell monolayers with an antibody directed at an N-terminal epitope of Connexin43 and analyzed its expression by immunocytofluorescence. Figure 1c depicts the localization of Connexin43 staining (green) with the plasma membrane visualized with the PKH26 dye that partitions into the lipid bilayer (red).…”

Section: Development Of Polyclonalmentioning

confidence: 99%

Bystander killing of malignant cells via the delivery of engineered thymidine-active deoxycytidine kinase for suicide gene therapy of cancer

Neschadim

Wang²,

Lavie

et al. 2012

Cancer Gene Ther

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Activity and specificity of chemotherapeutic agents against solid tumors can be augmented via the targeted or localized delivery of 'suicide' genes. Selective activation of specific prodrugs in cells expressing the 'suicide' gene drives their elimination by apoptosis, while also enabling the killing of adjacent bystander cells. Strong bystander effects can compensate for poor 'suicide' gene delivery, and depend on the prodrugs used and mechanisms for the acquisition of activated drug by the bystander population, such as the presence of gap junctional intercellular communications. Although a number of 'suicide' gene therapies for cancer have been developed and characterized, such as herpes simplex virus-derived thymidine kinase (HSVtk)-based activation of ganciclovir, their limited success highlights the need for the development of more robust approaches. Limiting activation kinetics and evolution of chemoresistance are major obstacles. Here we describe 'suicide' gene therapy of cancer based on the lentivirus-mediated delivery of a thymidine-active human deoxycytidine kinase variant. This enzyme possesses substrate plasticity that enables it to activate a multitude of prodrugs, some with distinct mechanisms of action. We evaluated the magnitude and mechanisms of bystander effects induced by different prodrugs, and show that when used in combination, they can synergistically enhance the bystander effect while avoiding off-target toxicity.

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

Abstract: 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.

Cited by 58 publications

References 16 publications

Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo

Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo

DU-145 prostate carcinoma cells that selectively transmigrate narrow obstacles express elevated levels of Cx43

Bystander killing of malignant cells via the delivery of engineered thymidine-active deoxycytidine kinase for suicide gene therapy of cancer

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