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Absence of cell communication for fluorescein and dansylated amino acids in an electrotonic coupled cell system.

Quantitative evaluation of the diffusion process of sodium fluorescein and dansylated amino acids in the salivary gland of the larvae of Drosophila hydei reveals that the differences in specific permeability between the junctional and nonjunctional membranes, as found for small ions, do not apply to the fluorescent probes. There are no significant differences between the permeability properties for the different dansylated amino acids tested, and the same properties are found for sodium fluorescein.

Animals↗

Oestriol and oestradiol increase cell to cell communication and connexin43 protein expression in human myometrium.

Oestradiol increases the protein expression of connexin43 (Cx43) gap junctions in myometrium but the effect of oestriol on gap junction expression has not been described previously. Oestriol is the most abundant free oestrogen in pregnant women and there is a marked surge in oestriol concentrations before term and idiopathic preterm labour. In order to determine whether oestriol may have a physiological action on the myometrium, cultured human myometrial cells obtained from non-pregnant hysterectomy specimens were exposed to 10 nmol/l oestradiol or oestriol. Intercellular communication between myometrial cells was investigated by microinjection of confluent cultured cells with the gap junction-permeant tracer Cascade Blue. There was a progressive increase in coupling after exposure to oestradiol or oestriol (P < 0.0005). An increase in Cx43 protein expression was demonstrated by immunocytochemistry after 1 h (P < 0.01) and 3 days (P < 0.01) exposure, and by Western blotting after 1 h (P < 0.01) and 3 days (P < 0.05) exposure, to both oestradiol and to oestriol. We conclude that oestriol increases gap junction communication in human myometrium by increasing gap junction expression. Elevated oestriol concentrations may thus play a role in the initiation of labour in women, by increasing cell-cell communication in the myometrium.

Adult↗

Modulation of cell-cell communication in the cause and chemoprevention/chemotherapy of cancer.

Chemopreventive or chemotherapeutic agents have been those that either kill cancer cells to a differential degree over the non-cancer cells or those chemicals that either block the induction of tumors in carcinogen-treated animals or retard transplanted tumors in animals. Carcinogenesis is a multi-stage, multi-mechanism process, involving the irreversible alteration of a stem cell ("initiation"), followed by the clonal proliferation of the initiated cell ("promotion"). To develop a strategy for intervention with chemoprevention/chemotherapeutic chemicals, the basic mechanism(s) of carcinogenesis must be understood. Gap junction intercellular communication (GJIC) regulates cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Normal cells have functional GJIC while cancer cells do not. Tumor promoters and oncogenes inhibit GJIC, while anti-tumor promoter and anti-oncogene drugs can reverse the down-regulation of GJIC. Transfection of gap junction genes (connexins) has been shown to reverse the tumorigenic phenotype. If prevention/treatment of cancer is to occur, prevention of the chronic down regulation of GJIC by tumor promoters in non-tumorigenic but initiated cells or the up-regulation of GJIC in stably down-regulated GJIC in tumor cells must occur to prevent or to treat cancers.

Anticarcinogenic Agents↗

A correlated study of metabolic cell communication and gap junction distribution in the adult frog lens.

By using low molecular weight dye injection and laser scanning confocal microscopy it has been possible to assess the degree of dye communication in several regions (intraepithelial, epithelium-fibre cell, fibre-epithelium and fibre-fibre) of the adult frog lens. These same areas of the lens have also been examined by freeze fracture electron microscopy for the presence and organisation of gap junctions. Epithelial cell lateral membranes have numerous gap junctions which efficiently transmitted dye to their neighbours though none was detectable in the underlying fibre cells. This was correlated with an apparent absence of gap junctions at the epithelium/fibre cell interface. Dye spread between cortical fibre cells was only observed in a subset of fibres in the bow region of the lens. Neither mature cortical fibres nor immature bow fibres appeared to be dye-coupled and we detected no dye passed from fibre cells to adjacent epithelial cells at their anterior ends. This pattern of dye communication was also correlated with the apparent absence of recognisable gap junctions on the lateral membranes of either the recently differentiated bow fibres or the mature cortical fibres. Classical gap junctions were only found on the membranes of fibres between five and ten cells in from the lens bow, i.e. the subset of fibres which were dye-coupled. No gap junctions were found between deeper cortical fibres or nuclear fibres, although they were characterised by a number of square arrays. Though electrically well coupled the adult frog lens may be relatively poorly dye coupled and this could depend on the age and differentiation stage of the cells concerned. The model of a freely communicating lens clearly requires re-examination by correlated physiological and morphological studies.

Animals↗

Cell-cell communication during double fertilization.

Double fertilization in flowering seed plants requires intercellular signaling events between many interacting partners. The four cell types of the seven-celled female gametophyte communicate with each other to establish and maintain their identity. They secrete signaling molecules to guide the male gametophyte and to mediate sperm cell discharge and transport towards the two female gametes (the egg and central cell). After fusion of the gametes, guidance signals have to be removed to prevent polyspermy, embryo and endosperm development is induced generating daughter cells or nuclear regions of a different fate, and cell death is induced in the surrounding ovular cells. Until recently, little was known about the molecular nature of the signaling molecules that are involved in these processes. Now, small secreted proteins and peptides have been identified as prime candidates mediating several of these communication events.

Cell Communication↗

Vanadium compounds promote the induction of morphological transformation of hamster embryo cells with no effect on gap junctional cell communication.

Vanadium compounds were found to promote the induction of morphological transformation of hamster embryo cells. Exposure of the cells to Na-O-vanadate, vanadin (V) oxide or vanadin (IV) oxide sulfate following pre-exposure to a low concentration of benzo[a]pyrene, potentiated the induction of transformed colonies similar to 12-O-tetradecanoylphorbol-13-acetate. Unlike this phorbol ester, vanadium compounds did not inhibit intercellular communication, or active protein kinase C. Nor did vanadate influence the reoccurrence of communication after removal of a communication blocking phorbol ester. On the other hand, vanadate showed strong synergism with the phorbol ester on induction of transformed morphology in the phorbol ester sensitive cell line BPNi. This suggests that vanadium and tumor promoting phorbol esters mediate their effect on the induction of morphological transformation of hamster embryo cells through different mechanisms.

Animals↗

The Sertoli-germ cell communication network in mammals.

As soon as scientists began to study testicular structure and function, the concept emerged that SCs and GCs communicate. We now know that the seminiferous epithelium is certainly one of the most complex tissues and that the structural and functional supports of SC-GC communication are extremely elaborate. At all stages of sexual maturation, somatic cells and GCs have developed a formidable set of communication devices that are involved in attachment, displacement, cell shaping, and cell-cell transfer of molecules and cellular materials. Some of the best morphologists since the nineteenth century have studied the anatomical basis of the SC-GC dialogue and have laid the foundations to the understanding of the spermatogenic process. Further experimental efforts are still being made. In particular, new data are emerging that have enabled scientists to go beyond the descriptional or deductive aspects and to tackle the mechanical aspects. From the functional point of view, significant progress has been made in deciphering SC-GC cell language. The unique strategic position of the SC allows this cell type to receive, integrate, and emit all the signals required for the spermatogenic process to or from the extratubular compartment (e.g., FSH, testosterone), the peritubular cells (e.g., P-Mod-S), and GCs themselves. Its location also allows it to coordinate GC activity in both the transversal and the longitudinal axes of the seminiferous tubule. The SC barrier and SC products create the physical and chemical microenvironments required for the completion of each of the different steps of spermatogenesis. In addition to the tubule fluid, the SC products directly or indirectly implicated in GC control are proteins, peptides, and steroid(s) involved in germ cell proliferation, differentiation, and metabolism; transport/binding proteins; proteases; extracellular matrix components; energy metabolites; antiproteases; and various membrane components. Sertoli cell polarization results from the existence of SC-SC occluding junctions. The products required for the mitotic phase of spermatogenesis may principally be secreted basally, whereas those required for meiotic division, spermiogenesis, and sperm cells may preferentially be secreted apically. The interaction between SC factors and GCs is mediated by GC membrane receptors and different endocytic processes. The GC secondary pathway(s) involved in SC action remains a mystery. Germ cell markers that would enable a precise assessment of SC influence are lacking. Changes in the composition of the GC complement and in GC size and shape, as well as GC divisions and migration, profoundly affect SC morphology and function.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Intercellular communications in cell differentiation and in hepatic carcinogenesis].

The liver epoch like other tissue epochs occurs after that different events have induced heterogeneity in embryonic cells which results in distinct evolutionary processes. These events and those of organogenesis like "induction" are deeply dependent on cell-cell communications. Cell-cell interactions involve either soluble factors (hormones, growth factors), extracellular matrix or plasma membrane proteins responsible for cell-cell recognition and/or adhesion. All these plasma membrane signals are transduced to the nucleus and modulate the expression of groups of genes. To be functionally stable along the adult stage the liver has to maintain an ordered activity of cell renewal. This balance between proliferation and differentiation is, at least in part, controlled by cell-cell communications. Therefore, it is not surprising that intercellular communications are altered during hepatocarcinogenesis. They involve changes in the distribution of junctions, in the amounts of extracellular matrix components and/or growth factors which all result in modifying the differentiation/proliferation balance. Cell culture models have been used for these different studies; new in vitro systems should be set up in the near future by taking advantage of the targeted hepatocarcinogenesis in transgenic mouse.

Adult↗

Molecules mediating cell-ECM and cell-cell communication in human heart valves.

The specific phenotype of different tissues depends on the interactions of cells with neighboring cells and the surrounding extracellular matrix, which is mediated by cell adhesion receptors including integrins, immunoglobulin family members, syndecans, and selectins. The aim of this study was to investigate the adhesion profile of native human valve interstitial cells (ICs) in situ and in vitro by analyzing these adhesion receptors. Flow cytometry and immunocytochemistry was used to quantify the expression of the specific receptors on ICs cultured from all human cardiac valves, and immunohistochemistry were used to profile their distribution pattern in valve tissue sections. The valve leaflets and cultured ICs from all valves expressed alpha1, alpha2, alpha3, alpha4, and alpha5 integrins to varying degrees and percentages with very little expression of alpha6 and alphaV. Valve leaflet ICs from all valves, expressed predominantly beta1 integrin but no beta3 or beta4 integrin. Syndecan-1 and Syndecan-4 were not detected. Intercellular adhesion molecule-1 was weakly detected, whereas vascular adhesion molecule-1 was barely detectable and E-selectin was not detected. This study has delineated the identity of some of the integrins synthesized and expressed by human valve ICs and the specificity of adhesion molecules with which the valve ICs interact with the extracellular matrix and mediate intercellular interactions. This pattern of expression of cell surface adhesion molecules may be considered as a basis for a fingerprint on which to base future cell alternatives and would provide useful information for valve tissue engineering.

Cell Adhesion↗

Extracellular matrix regulation of cell-cell communication and tissue-specific gene expression in primary liver cultures.

Epithelial-mesenchymal interactions are effected, in part, by extracellular matrix components. We have spent many years analyzing the influence of extracellular matrix, both as extracts of matrix and as purified matrix components, on the growth and differentiation of normal and neoplastic liver cells. Currently we are focused on analyzing the influence of the extracellular matrix components, glycosaminoglycans and proteoglycans. We have found that these factors induce dramatic morphological changes, are potent inducers of gap junction synthesis and can regulate tissue-specific gene expression. With respect to gap junctions: intercellular communication via gap junctions, as measured by dye and electrical coupling, disappears within 12 hrs in primary rat hepatocytes cultured in serum supplemented media or within 24 hrs in cells in a serum free, hormonally defined medium designed for hepatocytes. Glucagon and linoleic acid/BSA were the primary factors in the HDM responsible for the extended life span of the electrical coupling. Addition of proteoglycans or glycosaminoglycans to hormonally defined medium after 24 hrs resulted in reexpression of electrical and dye coupling when assayed at 96 hrs of culture. The incidence of coupling was less than 5% in hormonally defined medium alone. Coupling incidence increased to 10-30% with the addition of 10 micrograms/ml of glycosaminoglycans (i.e., hyaluronic acid, dermatan sulfate, chondroitin 4- or 6-sulfate, and iota- or kappa-carrageenan) to hormonally defined medium. By contrast, the same concentrations of chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, or lambda-carrageenan resulted in dye coupling in more than 70% of the cells, with numerous cells showing dye spread from a single injected cell (in the case of the proteoglycans). The greatest effect of those tested was elicited by the dermatan sulfate proteoglycans, which induced cell-cell communication in 90-100% of the cells. Heparins gave intermediate responses (30-50%). Western blots demonstrated that the amounts of the main intrinsic gap junction polypeptide (27 KDa) extractable from cells correlated with the degree of electrical and dye coupling. Thus, proteoglycans and glycosaminoglycans appear to elicit the formation and function of gap junctions and may thus play a role in the regulation of intercellular communication under normal and pathological conditions. With respect to gene expression: normal rat hepatocytes maintained in culture on tissue culture plastic and in serum supplemented medium lose their tissue-specific functions within hours to a few days due to loss of synthesis and to rapid degradation of tissue-specific mRNAs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗