Altered gap junctional intercellular communication in neoplastic rat esophageal epithelial cells

Abstract

Gap junctional intercellular communication (GJIC) is reduced in many neoplastic cells, but few data exist for esophageal neoplasms. GJIC was examined by fluorescent dye microinjection in two nontumorigenic and two highly tumorigenic rat esophageal epithelial cell lines. All lines expressed high levels of dye coupling in homologous cell culture. In cocultures of nontumorigenic and tumorigenic cells, however, only one of six cell combinations displayed significant heterologous GJIC. Northern, Western, and immunohistochemical analyses indicated that all four cell lines expressed comparable levels of connexin43 (Cx43), but not connexin32 or connexin26, and formed Cx43-containing gap junction plaques at cell-cell interfaces. Immunostaining of rat esophageal frozen sections demonstrated that esophageal epithelial cells expressed Cx43 in vivo. In normal epithelium, the highest expression was seen in the basal cells and little suprabasal staining was evident. In preneoplastic and neoplastic lesions of the esophageal epithelium which were induced by treating rats with N-nitrosomethylbenzylamine, Cx43 staining of the basal layer was also seen but appeared to be more diffuse compared to normal epithelium. In addition, suprabasal Cx43 staining was apparent in dysplastic and papillomatous lesions. These results indicate that Cx43 is expressed in normal and neoplastic rat esophageal cells and that the cells exhibit extensive homologous GJIC, but little heterologous GJIC. This lack of heterologous GJIC may be due to differences in cell adhesion proteins or other factors.

Neoplastic phenotype of gap-junctional intercellular communication–deficient WB rat liver epithelial cells and its reversal by forced expression of connexin 32

“…Previous connexin transfection/ transduction and connexin antisense studies [13][14][15][16][17][18][19][20][21][22][23], however, provided direct evidence to the contrary. In addition, studies from several groups indicated that neoplastic cells can express functional gap junctions among themselves (homologous GJIC) but be incapable of forming gap junctions with normal cells (heterologous GJIC) [37][38][39][40]. As Loewenstein [7] first noted, neoplastic cells may manifest defective GJIC in several ways including the lack of gap junctions or the formation of gap junctions with reduced channel permeability, the inability to form gap junctions with normal cells (lack of heterologous GJIC), and the inability to respond to junctional signal molecules.…”

Cell-Cell Communication in the Tumor Microenvironment, Carcinogenesis, and Anticancer Treatment

“…The glycocalyx encompasses five different classes of adhesion molecules (immunoglobulins, integrins, cadherins, selectins, and cell adhesion molecules) that directly connect it to the ECM [2]. Furthermore, the glycocalyx of the plasma membrane directly influences the ability of cells to form gap junction channels [115], reviewed in [116]. In this manner, the glycocalyx itself influences how information is filtered and forwarded.…”

Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells

“…2 cx43 is a tumor-suppressor gene. 1,3,4 Expression of cx43 is reduced in human mammary carcinoma, 5,6 prostate cancer, 7,8 human glioblastoma, 4,9 skin squamous-cell carcinoma, 10 lung-cancer cells, [11][12][13] esophageal cancer cells 14,15 and human mesothelioma. 16 Transfection of cx43 restored several "normal" phenotypes to neoplastic cells, including rat C6 glioma, 17,18 human mammary carcinoma, 19 human glioblastoma, 4 transformed dog kidney epithelial cells, 3 rhabdomyosarcoma cells 20 and lung-cancer cells.…”