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PubMed1998

Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration.

Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane-membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.

Amino Acid Sequence↗
PubMed1997

Blocking gap junctional intercellular communication in myoblasts inhibits myogenin and MRF4 expression.

Cells rely heavily on cues from their extracellular environment and other cells to coordinate normal physiological processes, and the exchange of molecules via gap junctions has been suggested as on important avenue for cell-cell communication. Gap junctions are found in virtually all mammalian tissues with the notable exception of adult skeletal muscle. However, since functional gap junctions have been detected during the early stages of muscle development, gap junctional intercellular communication (GJIC) may play on important role in myogenesis. In this study, GJIC in normal 16 myoblasts was inhibited using the known blockers l-octanol and beta-glycyrrhetinic acid (beta-GA). Under differentiation promoting conditions, 16 cells fused to form multinucleated myotubes, but when treated with either octanol or beta-GA, no fusion was observed. The expression of two muscle regulatory factors (MRFs), myogenin and MRF4, was examined in both the blocked and control cells. As expected, the activation of both the myogenin and MRF4 genes coincided with the onset of differentiation in the control 16 cells. Neither of these genes were turned on in the blocked cells, even when grown under low serum conditions. This inhibition of differentiation by octanol and beta-GA was reversible, since the activation of both MRF genes as well as myoblast fusion were observed when the blocking medium was replaced with normal differentiating medium. These results suggest that intercellular communication via gap junctions plays an important role in skeletal muscle development and perhaps in the cell signaling events that trigger the activation of muscle-specific MRF genes.

1-Octanol↗
PubMed2003

Modulation of homologous gap junctional intercellular communication of human dermal fibroblasts via a paracrine factor(s) generated by squamous tumor cells.

Loss of gap junctional intercellular communication (GJIC) is a characteristic of cancer cells. Since a coordinated interaction of epithelial tumor cells with stromal cells is a prerequisite for tumor invasion and metastasis, the present study was designed to test the hypothesis that skin-derived tumor cells may modulate homologous and heterologous GJIC. While homologous GJIC of human dermal fibroblasts as well as epidermal keratinocytes was detected, no communication was measured between SCL-1 cells derived from squamous cell carcinoma of human skin. Interestingly, co-cultures of dermal fibroblasts and SCL-1 tumor cells in serum-containing medium resulted in a 52-70% lowering of the number of communicating fibroblasts. Furthermore, incubation of confluent fibroblast cultures with serum-free supernatant fractions (20-30 kDa) from tumor cells, termed the 20/30 fraction, lowered the homologous gap junction communication of fibroblasts by >90%. This novel aspect of down-regulated homologous GJIC of dermal fibroblasts, which is reversible, was neither mediated by alteration of the expression of connexin43, the major gap junctional protein of dermal fibroblasts, nor by aberrant localization of connexin43 in the plasma membrane. Furthermore, post-translational modifications of connexins, such as phosphorylation, was not measured by mobility shift studies. Tumor cell-mediated GJIC down-regulation between fibroblasts was suppressed using EGTA-containing serum-free tumor cell-derived supernatants suggesting that calcium ions (Ca2+) might mediate the transduction of this effect. The involvement of Ca2+ in down-regulation of homologous GJIC of fibroblasts was supported by an increase in fluorescence intensity of the intracellular calcium-sensitive indicator Fura-2 upon treatment of fibroblasts with the active 20/30 fraction. In conclusion, these data establish homologous GJIC of (stromal) fibroblasts as a parameter modulated by a paracrine acting factor(s) of epithelial tumor cells during tumor-stroma interaction of skin cells.

Base Sequence↗
PubMed2003

[Effects of lovastatin on proliferation and gap junctional intercellular communication of human breast cancer cell MCF-7].

BACKGROUND & OBJECTIVE: Lovastatin,an inhibitor of endogenous cholesterol biosynthesis,has been widely used in the clinical treatment of hypercholesterolemia.Recently,lovastatin has been paid more attention for its wide-range effects on human cancer cells; however,the detail mechanisms of its anti-cancer effects are not yet understood. This study was designed to investigate the effects of lovastatin on proliferation and gap junctional intercellular communication (GJIC) of MCF-7 human breast cancer cells. METHODS: After treated with lovastatin at dosages of 4,8,16 micromol/L for 1-3 days,the cell differentiation was examined with nitroblue tetrazolium (NBT) reduction test;the proliferation and distribution of cell cycles were examined with flow cytometry (FCM). Meanwhile,GJIC of MCF-7 cells was observed using the scrape-loading and dye transfer(SLDT) technique. RESULTS: Lovastatin could inhibit the proliferation of MCF-7 cells significantly and 75.80 percent of cells were inhibited after treated with 16 micromol/L lovastatin for 72 hours (P< 0.05). Meanwhile, lovastatin could arrest MCF-7 cells in the G(0)/G(1) phase of cell cycle and 80 percent of cells were arrested in G(0)/G(1) phase after treated with lovastatin for 72 hours. Furthermore, lovastatin could induce the differentiation of MCF-7 cells (P< 0.01) and up-regulate GJIC in MCF-7 cells. After treated with 16 micromol/L lovastatin for 72 hours, transfer of LY fluorescence could reach 4-5 rows of cells from the scraped line. However, apoptosis in MCF-7 cells was not obvious. All these effects of lovastatin were in a dose-and time-dependent manner. CONCLUSION: It suggests that lovastatin has the capabilities of inhibiting proliferation, arresting MCF-7 cells at G(0)/G(1) phase of cell cycle and inducing differentiation. These effects of lovastatin maybe correlate with lovastatin promoting GJIC function in MCF-7 cells.

Antineoplastic Agents↗
PubMed2000

Exploring the relationship between the inhibition of gap junctional intercellular communication and other biological phenomena.

The mechanistic relationship of the inhibition of gap junctional intercellular communication (GJIC) to other toxicological phenomena was explored using a recently developed method that models the properties of a large population of molecules chosen to represent the 'universe of chemicals'. The analyses indicate that inhibition of GJIC is strongly linked to the carcinogenic process in rodents, to cellular but not systemic toxicity, to biological phenomena that may involve inflammatory processes and to development effects. The inhibition of GJIC appears not to be associated with genotoxic mechanisms. With respect to cancer causation, integration of the analyses suggests that inhibition of GJIC is involved in non-genotoxic cancer induction or in the non-genotoxic phases of the carcinogenic process (such as inflammation, cell toxicity, cell proliferation, inhibition of cell differentiation and apoptosis).

Animals↗
PubMed1994

Inhibition of gap-junctional intercellular communication by outdoor and indoor airborne particulate matter.

The inhibition of gap-junctional intercellular communication (GJIC) by different airborne particulate matter (APM) extracts was tested in V79 cells and in primary cultures of alveolar type II cells. The results show that extracts of APM were able to inhibit GJIC in V79 and in alveolar type II cells at non-cytotoxic doses. Chemical fractionation of extracts showed that the neutral fractions accounted for most of the inhibitory activity on GJIC. The activities of basic and acid fractions was less than 5% of the total activity. Polycyclic aromatic hydrocarbons and nitrated derivatives are unlikely to be responsible for the activity of the neutral fractions, because several representatives of these compounds failed to inhibit GJIC. Taken together, these results suggest that extracts of APM, in addition to the genotoxic activity that has been known for many years, also have a tumor promoting activity.

Air Pollutants↗
PubMed1998

Changes in the gap junctional intercellular communication in renal tubular epithelial cells in vitro treated with renal carcinogens.

Gap junctional intercellular communications (GJIC) are known as the channels for the direct transfer of cytoplasmic molecules between neighboring cells and are lost during transformation of normal cells. To study the function and the molecular mechanism for the loss of GJIC, the effects of dimethylnitrosamine, KBrO3 and FeSO4 x 7H2O, which are known as chemical tumor promoters of the kidney on the GJIC function and the expression of connexin 43 of Madin-Darby canine kidney (MDCK) epithelial cells, were examined. These tumor promoters inhibited the GJIC in MDCK cells. The expression of connexin 43 mRNA and connexin 43 protein was not altered by these treatments, whereas immunocytochemical study revealed that the distribution of connexin 43 protein was changed from the cell surface to the cytoplasma. These data suggest that blockage of GJIC in MDCK cells treated with renal carcinogens support the hypothesis that loss of GJIC might be important in renal carcinogenesis.

Animals↗
PubMed2000

Cadmium decreases gap junctional intercellular communication in mouse liver.

Cadmium (Cd) is an environmental pollutant of increasing importance, due to industrialization, smoking, and the lack of effective therapy for Cd poisoning. The general population is exposed to Cd principally through food and water. The metal accumulates slowly in the liver and kidney, the target organs of acute and chronic Cd toxicity, respectively. We showed recently that liver is also a target organ for chronic Cd toxicity. Gap junctional intercellular communication (GJIC) is a means of maintaining cellular homeostasis in multicellular organisms. It involves the transfer of small, water-soluble molecules through intercellular channels (gap junctions), composed of proteins called connexins. The major connexins of liver (hepatocytes) are connexin 32 (Cx32) and connexin 26 (Cx26). Cd disrupts cellular homeostasis in the liver through its induction of necrosis, apoptosis, and cellular proliferation. It is to be expected, therefore, that Cd must exert some effect on GJIC. This study investigates Cd-induced alterations in GJIC, Cx32, and Cx26 expression, and in cytoskeletal actin, and relates the changes to apoptosis and cell proliferation induced by Cd in vivo. Mice were injected ip with 30 micromol Cd/kg, and were observed for up to 48 h. Other groups of mice were injected with 5-60 micromol Cd/kg and observed for 9 h. Blood and liver were harvested and used for analysis of GJIC, connexin expression, cytoskeletal actin, serum enzymes, and liver pathology. Cd produced a time- and dose-dependent inhibition of GJIC in liver, along with parallel decreases in the expression of Cx32 and Cx26. Cd also produced disruption and loss of cytoskeletal actin in liver in a time- and dose-dependent manner. These observations are discussed in relation to the toxicity of Cd, and possible mechanisms of induction of the GJIC-related alterations are presented.

Animals↗
PubMed2003

High glucose alters connexin 43 expression and gap junction intercellular communication activity in retinal pericytes.

PURPOSE: To investigate the role of the gap junction protein, connexin-43 (Cx43) in the maintenance of retinal vascular homeostasis in diabetic retinopathy. METHODS: In human retinal pericytes (HRPs) and bovine retinal pericytes (BRPs) grown for 7 days in normal (5 mM) or high (30 mM)-glucose medium, the Cx43 protein level was determined by Western blot analysis. Parallel experiments were performed in HRPs to determine the Cx43 mRNA level by RT-PCR, the distribution and localization of Cx43 protein by immunostaining, and gap junction intercellular communication (GJIC) activity by a scrape-loading dye transfer technique. Distribution and localization of Cx43 protein was also determined in pericyte-endothelial cell cocultures. RESULTS: Western blot analysis of the Cx43 protein level in HRPs and BRPs indicated reduced Cx43 expression in the high-glucose condition (69.1% +/- 17% of control, P = 0.004; 62.3% +/- 19% of control, P = 0.001, respectively). The Cx43 mRNA level in HRPs grown in high-glucose medium also showed significant reduction (71.4% +/- 16.8% of control, P = 0.02). The relative number of Cx43 plaques indicative of Cx43 localization at specific sites of contact between adjacent cells showed significant reduction in the high-glucose condition (61% +/- 10% of control, P = 0.002); similarly, a significant reduction in the number of plaques was observed in cocultures grown in high-glucose medium compared with those in normal medium (59.4% +/- 29% of control, P = 0.001). Cells with reduced Cx43 expression showed significantly reduced transfer of lucifer yellow (61% +/- 13% of control, P = 0.001; r = 0.9). CONCLUSIONS: High-glucose-induced downregulation of Cx43 expression and inhibition of GJIC in retinal pericytes may play a role in the disruption of vascular homeostasis in diabetic retinopathy.

Animals↗
PubMed2003

[Effect of some polycyclic aromatic hydrocarbons on gap junction intercellular communication in hepatoma Hep G2 cell culture].

Systems regulating tissue homeostasis are gap junction intercellular communications (GJIC). It is accepted that the down-regulation of GJIP has been due to tumor promoting properties of carcinogens. In this study, effects of some carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons (PAH) on GJIC were investigated. Noncarcinogenic PAHs do not influence GJIC function. In dose 5 microg/ml carcinogenic PAHs down-regulated GJIC by 70-100% after a 24 h treatment. Dependent on the structure of PAHs, down-regulation was observed after a 1 h treatment. The methyl group in PAH structure decreased down-regulation of GJIC in 1 h experiments, whereas after a 24 h treatment the down-regulation caused by methyl group either contained or not contained PAH was nearly the same. To clarify the role of Ah-receptor in PAH action on GJIC, the effect of 2,3,7,8-tetrachlorodibezdioxin, a specific ligand of Ah-receptor was studied, which appeared to be insignificant. Benzo/a/pyrene does not influence the functioning of gramicidine channels formed in the phospholipid membrane. This result indicates that PAH action on GJIC is not associated with non-specific destruction of the membrane. Thus, two steps are there in PAH action on GJIC: one is fast and caused by specific interaction of unchanged PAH molecule, the other develops in time and is presumably associated with the formation of active metabolites.

Carcinogens↗
PubMed1999

Gap junctional intercellular communication and connexin43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro.

Gap junctional intercellular communication (GJIC) and the expression of gap junction proteins (connexins) are frequently decreased in neoplastic cells and have been increased by cAMP and retinoids. GJIC and connexin expression were investigated in early passage normal human ovarian surface epithelial (HOSE) cells, human ovarian adenocarcinoma cell lines (CaOV-3, NIH:OVCAR-3, SK-OV-3 and SW626) and surgical specimens of human serous cystadenocarcinomas. We hypothesized that GJIC and connexin expression would be decreased in neoplastic cells and would be increased by cAMP and retinoic acid. Cultured HOSE cells exhibited extensive fluorescent dye-coupling and connexin43 (Cx43) expression; other connexins were not detected. The ovarian adenocarcinoma cell lines had little dye-coupling or connexin expression. Deletions and rearrangements of the Cx43 gene were not detected by Southern blotting in the carcinoma lines. N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate and all-trans-retinoic acid inhibited cell proliferation, but did not enhance GJIC or Cx43 expression. Surface epithelial cells of benign ovaries expressed Cx43, but this expression was barely detectable in ovarian serous cystadenocarcinomas. Thus, normal HOSE cells had extensive GJIC and Cx43 expression whereas ovarian carcinoma cells had less and cAMP and retinoic acid did not change these, although both agents inhibited cell growth.

Adenocarcinoma↗
PubMed2003

Inhibition of mouse hepatocyte gap junctional intercellular communication by phenobarbital correlates with strain-specific hepatocarcinogenesis.

The inhibition of gap junctional intercellular communication (GJIC) is a common effect of nongenotoxic carcinogens and might be a biomarker for these agents. To further test this relationship, we hypothesized that phenobarbital would inhibit mouse hepatocyte GJIC and this would correlate with strain-specific hepatocarcinogenicity. Phenobarbital is a strong nongenotoxic hepatocarcinogen in B6C3F1 mice, but not in C57BL/6 mice. Hepatocytes were isolated from males of both strains, placed in coculture with rat liver epithelial cells, and treated with phenobarbital for up to 14 days. Male mice were also administered PB by single intraperitoneal injection (0.1 mg/kg), then sacrificed 24 h later, or given phenobarbital in the drinking water (500 ppm) for 14 days before sacrifice. GJIC was assayed in cocultures by fluorescent dye microinjection and in isolated liver tissue by fluorescent dye "cut-loading." Phenobarbital decreased GJIC only in cultured B6C3F1 hepatocytes; this was dose-responsive and temporary, because hepatocyte GJIC returned to control levels within 24 h of phenobarbital exposure. Administration of phenobarbital to mice for 14 days also decreased hepatocyte dye coupling in B6C3F1 liver, but this effect was not seen in C57BL/6 mice or observed after a single administration of the drug. Phenobarbital did not alter connexin32 and connexin26 expression, but increased hepatic Cyp2b1 expression and the liver weight:body weight ratio in both strains. In summary, phenobarbital inhibited mouse hepatocyte GJIC in vivo and in vitro and in correlation with strain-specific hepatocarcinogenicity. These data support the hypothesis that decreased GJIC is a biomarker for nongenotoxic carcinogens and involved in their carcinogenic mechanism.

Administration, Oral↗
PubMed2003

Epigenetic properties of the diarrhetic marine toxin okadaic acid: inhibition of the gap junctional intercellular communication in a human intestine epithelial cell line.

Okadaic acid (OA) is produced by several types of dinoflagellates (marine plankton) and has been implicated as the causative agent of diarrhetic shellfish syndrome. Previous studies have shown that okadaic acid is a tumor promoter and a specific potent inhibitor of protein phosphatases and protein synthesis. These effects in turn affect intracellular processes such as metabolism, contractility, gene transcription, and the maintenance of cytoskeletal structure. Gap junctional intercellular communication (GJIC) is a means of maintaining cellular homeostasis in organs, the disruption of which favors tumor cell growth. The GJIC involves the transfer of small water-soluble molecules through intercellular channels (gap junctions), composed of proteins called connexins. OA disrupts cellular homeostasis in Caco-2 cells through several mechanisms including protein synthesis inhibition, apoptosis, and clastogenic effects. The aim of this study was then to evaluate the expression of the connexin 43 (Cx 43) mRNA in relation with the cytotoxicity induced by OA (3.75-60 ng/ml) in a human colonic epithelial cell line in culture (Caco-2 cells). OA produced a dose-dependent inhibition of GJIC in Caco-2 cells, along with a parallel decrease in the expression of Cx 43 as shown by immunohistochemistry using anti-Cx 43 antibody. Since Cx 43 is implicated in the suppression of tumors and OA is a tumor promoter, the inhibition of GJIC may play an important role in its carcinogenesis. These data are discussed in relation to the toxicity of OA, total RNA synthesis, and possible specificity of Cx 43 inhibition in the GJIC.

Caco-2 Cells↗
PubMed2002

Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication.

The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast tumor cells were found to exhibit diverse gap junction phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of Cx43 and sparse intercellular communication (MDA-MB-231); and (c) significant levels of Cx43 and moderate intercellular communication (Hs578T). Although retroviral delivery of Cx43 and Cx26 cDNAs to MDA-MB-231 cells did not achieve an expected substantial rescue of intercellular communication, overexpression of connexin genes did result in a dramatic suppression of tumor growth when connexin-expressing MDA-MB-231 cells were implanted into the mammary fat pad of nude mice. Subsequent immunolocalization studies on xenograph sections revealed only cytoplasmic stores of Cx43 and no detectable gap junctions. Moreover, DNA array and Western blot analysis demonstrated that overexpression of Cx43 or Cx26 in MDA-MB-231 cells down-regulated fibroblast growth factor receptor-3. Surprisingly, these results suggest that Cx43 and Cx26 induce their tumor-suppressing properties by a mechanism that is independent of significant gap junctional intercellular communication and possibly through the down-regulation of key genes involved in tumor growth. Moreover, our studies show that retroviruses are effective vehicles for delivering connexins to human breast tumor cells, facilitating potential gene therapy applications.

Animals↗
PubMed1993

Phosphatase inhibitors, gap junctional intercellular communication and [125I]-EGF binding in hamster fibroblasts.

A number of phosphatase inhibitors (okadaic acid, calyculin A, aluminium fluoride, sodium molybdate, sodium orthovanadate, pervanadate and vanadyl sulphate) were investigated for their effects on gap junctional intercellular communication (GJIC) and [125I]-epidermal growth factor (EGF) binding in early passage Syrian hamster embryo cells (mainly fibroblast-like cells) and in V79 Chinese hamster lung fibroblasts. Only pervanadate decreased GJIC significantly. After the initial pervanadate-induced decrease the GJIC recovered rapidly. Only pervanadate was able to change the band pattern of the gap junction protein connexin43 (cx43) in Western blots. Together this may indicate either that there is a low turnover of phosphate groups in cx43 under basal conditions or that the putative phosphatases are not sensitive to most of the phosphatase inhibitors applied. In contrast, pervanadate, orthovanadate and molybdate decreased [125I]-EGF binding. 12-O-Tetradecanoylphorbol-13-acetate (TPA) is able to induce the phosphorylation of both cx43 and the EGF receptor, concomitantly with a decrease in GJIC and [125I]-EGF binding. These effects are reversible after removal of TPA. It could be imagined that other phosphatases would act on cx43 and the EGF receptor after the forced phosphorylation of the two molecules. Thus TPA was used to downregulate GJIC and [125I]-EGF binding and phosphatase inhibitors were applied in the upregulation phase. Only pervanadate affected the upregulation of GJIC, and pervanadate, orthovanadate and molybdate affected the upregulation of [125I]-EGF binding. Thus it is not an identical complement of phosphatases that act on cx43 and the EGF receptor. All the downregulating agents are assumed to be phosphotyrosine phosphatase inhibitors.

Aluminum Compounds↗
PubMed1982

Alterations in intercellular junctions of the uterine epithelium during the preimplantation phase in the rabbit.

In the rabbit, the pseudopregnant uterus has been used as a model for studying alterations characteristic of the preimplantation phase. Alterations in intercellular junctions of the uterine epithelium were investigated during early pseudopregnancy (day 0 to day 6) by means of the freeze-fracture technique. In the uterine epithelium of oestrous females the zonula occludens belongs to the "tight" type of tight junctions. During pseudopregnancy an impressive proliferation of tight junctional belts can be observed. The basal strands proliferate, forming loops perpendicular to the luminal surface, whereas the more or less parallel arrangement of the luminal strands is maintained. At day 4 of pseudopregnancy macular tight junctions begin to develop on the lower portions of the lateral plasmalemma and are extensive by day 6 post hCG. Small gap junctions are infrequent between cells of the uterine epithelium and show no significant changes during the preimplantation phase. The physiological significance of the present morphological observations is discussed in the light of changes occurring during the preimplantation period.

Animals↗
PubMed1999

Phosphatases involved in modulation of gap junctional intercellular communication and dephosphorylation of connexin43 in hamster fibroblasts: 2B or not 2B?

12-O-Tetradecanoylphorbol-13-acetate (TPA) caused strong suppression of gap junctional intercellular communication, altered phosphorylation status of the gap junction protein, connexin43, and disappearance of immunorecognizible connexin43-containing gap junction plaques in V79 fibroblasts. When TPA was removed, all parameters normalized during a 3- to 4-h period. The normalizations were independent of protein synthesis, suggesting the possible involvement of phosphatases. None of the phosphatase inhibitors okadaic acid, calyculin A, cyclosporin A, or FK506 affected intercellular communication or connexin43 phosphorylation status on their own. In sequential exposures to TPA and phosphatase inhibitors, only the protein-phosphatase 2B (PP2B) inhibitors cyclosporin A and FK506 delayed the recovery of the studied parameters. Rapamycin binds to the same set of proteins as does FK506, but without inhibiting PP2B. Rapamycin did not affect the recovery of intercellular communication, but it delayed the normalization of connexin43 band pattern and immunorecognition of gap junction plaques. Dephosphorylation of immunoprecipitated connexin43 was studied using PP1, 2A, 2B, and 2C. PP2A was the most efficient (by 100-fold on a molar basis). Connexin43 immunoprecipitated from TPA-exposed cells was a poor substrate for PP1, 2B, and 2C. Thus, PP2B appeared to play a role in normalization of intercellular communication, but not necessarily in direct dephosphorylation of connexin43. Peptidyl-prolyl isomerase activity of cyclosporin/FK506/rapamycin-binding proteins may promote the dephosphorylation of connexin43 in cells.

Animals↗
PubMed1988

Freeze-fracture study of intercellular junctions in benign and malignant mesothelial cells in effusions and a comparison with those seen in pleural mesotheliomas (solid tumour).

This study involves an analysis by thin section and freeze-fracture techniques of the intercellular junctions of exfoliated benign and malignant mesothelial cells obtained from 4 cases, two benign and two malignant effusions. Pleural biopsies (solid tumours) of two further cases of confirmed epithelial malignant mesotheliomas were also studied to compare the organization, distribution and characteristics of the tight junctions, gap junctions and desmosomes observed between the three groups of cases. The results showed that both tight and gap junctions varied greatly in their organization in the exfoliated benign and malignant mesothelial cells. However they were often large and very well developed. In contrast, the tight and gap junctions in the solid tumours were considerably reduced both in their size and frequency, a feature which is well recognized in the literature as consistent with the neoplastic process. Our observation of florid tight and gap junctions in the exfoliated benign and malignant mesothelial cells, raises some important aspects of behaviour of neoplastic cells in effusion fluid. It is our opinion that cells in the fluid are exposed to microenvironmental influences which are quite distinct from those in a 'solid' tumour. We suggest that alteration in the binding sites of the extracellular matrix molecules, their influence on the cytoskeleton and the consequent effect on the development of tight and gap junctions are important factors which need further elucidation. The most significant feature of this study is however the demonstration of essential differences in the cell junctional characteristics between neoplastic mesothelial cells in body cavity fluids and those in tissues thus emphasizing the importance of environmental influences in the development of a neoplasm and its spread.

Adult↗