The Role of Altered Cell–Cell Communication in Melanoma Progression

Under normal homeostasis, melanocyte growth and behaviour is tightly controlled by the surrounding keratinocytes. Keratinocytes regulate melanocyte behaviour through a complex system of paracrine growth factors and cell-cell adhesion molecules. Pathological changes, leading to development of malignant melanoma, upset this delicate homeostatic balance and can lead to altered expression of cell-cell adhesion and cell-cell communication molecules. In particular, there is a switch from the E-cadherin-mediated keratinocyte-melanocyte partnership to the N-cadherin-mediated melanoma-melanoma and melanoma-fibroblast interaction. Other changes include the alteration in the gap junctions formed between the melanocyte and keratinocyte. Changes in the connexin expression, in particular the loss of connexin 43, may result in a reduction or a loss of gap junctional activity, which is thought to contribute towards tumour progression. In the current review we describe the alterations in cell-cell adhesion and communication associated with melanoma development and progression, and discuss how a greater understanding of these processes may aid the future therapy of this disease.     

Effect of X-Irradiation at Different Stages in the Cell Cycle on Individual Cell–Based Kinetics in an Asynchronous Cell Population

Using an asynchronously growing cell population, we investigated how X-irradiation at different stages of the cell cycle influences individual cell–based kinetics. To visualize the cell-cycle phase, we employed the fluorescent ubiquitination-based cell cycle indicator (Fucci). After 5 Gy irradiation, HeLa cells no longer entered M phase in an order determined by their previous stage of the cell cycle, primarily because green phase (S and G2) was less prolonged in cells irradiated during the red phase (G1) than in those irradiated during the green phase. Furthermore, prolongation of the green phase in cells irradiated during the red phase gradually increased as the irradiation timing approached late G1 phase. The results revealed that endoreduplication rarely occurs in this cell line under the conditions we studied. We next established a method for classifying the green phase into early S, mid S, late S, and G2 phases at the time of irradiation, and then attempted to estimate the duration of G2 arrest based on certain assumptions. The value was the largest when cells were irradiated in mid or late S phase and the smallest when they were irradiated in G1 phase. In this study, by closely following individual cells irradiated at different cell-cycle phases, we revealed for the first time the unique cell-cycle kinetics in HeLa cells that follow irradiation.     

Cell Bound α-Amylase in Aspergillus oryzae

It was previously reported that α-amylase accumulation is caused within the mycelium grown in a phosphate deficient medium and the concentration of anions or pH in a surrounding medium is responsible for its liberation. As it was subsequently found that α-amylase liberation from the mycelium of Aspergillus oryzae is stimulated by peptone, an attempt was made on purification of effective substances from it. The present paper describes on purification and properties of phosphopeptides found as an effective substance for α-amylase liberation, and discusses on the stimulation effect, comparing with the effects on pH and concentration of anions which were previously observed.     

Influenza Hemifusion Phenotype Depends on Membrane Context: Differences in Cell–Cell and Virus–Cell Fusion

Influenza viral entry into the host cell cytoplasm is accomplished by a process of membrane fusion mediated by the viral hemagglutinin protein. Hemagglutinin acts in a pH-triggered fashion, inserting a short fusion peptide into the host membrane followed by refolding of a coiled-coil structure to draw the viral envelope and host membranes together. Mutations to this fusion peptide provide an important window into viral fusion mechanisms and protein–membrane interactions. Here, we show that a well-described fusion peptide mutant, G1S, has a phenotype that depends strongly on the viral membrane context. The G1S mutant is well known to cause a “hemifusion” phenotype based on experiments in transfected cells, where cells expressing G1S hemagglutinin can undergo lipid mixing in a pH-triggered fashion similar to virus but will not support fusion pores. We compare fusion by the G1S hemagglutinin mutant expressed either in cells or in influenza virions and show that this hemifusion phenotype occurs in transfected cells but that native virions are able to support full fusion, albeit at a slower rate and 10–100 × reduced infectious titer. We explain this with a quantitative model where the G1S mutant, instead of causing an absolute block of fusion, alters the protein stoichiometry required for fusion. This change slightly slows fusion at high hemagglutinin density, as on the viral surface, but at lower hemagglutinin density produces a hemifusion phenotype. The quantitative model thus reproduces the observed virus–cell and cell–cell fusion phenotypes, yielding a unified explanation where membrane context can control the observed viral fusion phenotype.     

Cell—cell interactions in bacterial populations

In developing bacterial populations many essential processes, such as division, genetic transformation, sporulation, and synthesis of antibiotics and secondary metabolites, are regulated by intercellular communication mediated by secretion of signaling molecules, such as homoserine lactones and peptides. Another intercellular communication type, namely a physical contact between cells (cell aggregation), plays a key role in formation of biofilms or cellular consortia and in cell proliferation under unfavorable conditions. The mechanisms involved in these two types of bacterial communication are discussed in this review.Translated from Biokhimiya, Vol. 69, No. 11, 2004, pp. 1555–1564.Original Russian Text Copyright © 2004 by Voloshin, Kaprelyants     

Quantification of Biomass and Cell Motion in Human Pluripotent Stem?Cell?Colonies

Somatic cell reprogramming to pluripotency requires an immediate increase in cell proliferation and reduction in cell size. It is unknown whether proliferation and biomass controls are similarly coordinated with early events during the differentiation of pluripotent stem cells (PSCs). This impasse exists because PSCs grow in tight clusters or colonies, precluding most quantifying approaches. Here, we investigate live cell interferometry as an approach to quantify the biomass and growth of HSF1 human PSC colonies before and during retinoic acid-induced differentiation. We also provide an approach for measuring the rate and coordination of intracolony mass redistribution in HSF1 clusters using live cell interferometry images. We show that HSF1 cells grow at a consistent, exponential rate regardless of colony size and display coordinated intracolony movement that ceases with the onset of differentiation. By contrast, growth and proliferation rates show a decrease of only ∼15% decrease during early differentiation despite global changes in gene expression and previously reported changes in energy metabolism. Overall, these results suggest that cell biomass and proliferation are regulated independent of pluripotency during early differentiation, which is distinct from what occurs with successful reprogramming.     

Developmental and Stress-Induced Remodeling of Cell–Cell Communication in the Adrenal Medullary Tissue

The adrenal medullary tissue contributes to maintain body homeostasis in reaction to stressful environmental changes via the release of catecholamines into the blood circulation in response to splanchnic nerve activation. Accordingly, chromaffin cell stimulus-secretion coupling undergoes temporally restricted periods of anatomo-functional remodeling in response to prevailing hormonal requirements of the organism. The postnatal development of the adrenal medulla and response to stress are remarkable physiological situations in which the stimulus-secretion coupling is critically affected. Catecholamine secretion from rat chromaffin cells is under a dual control involving an incoming initial command arising from the sympathetic nervous system that releases acetylcholine at the splanchnic nerve terminal-chromaffin cell synapses and a local gap junction-mediated intercellular communication. Interestingly, these two communication pathways are functionally interconnected within the gland and exhibit coordinated plasticity mechanisms. This article reviews the physiological and molecular evidence that the adrenal medullary tissue displays anatomical and functional adaptative remodeling of cell–cell communications upon physiological (postnatal development) and/or physiopathological (stress) situations associated with specific needs in circulating catecholamine levels.     

Cell–cell Signaling in the Neurovascular Unit

Historically, the neuron has been the conceptual focus for almost all of neuroscience research. In recent years, however, the concept of the neurovascular unit has emerged as a new paradigm for investigating both physiology and pathology in the CNS. This concept proposes that a purely neurocentric focus is not sufficient, and emphasizes that all cell types in the brain including neuronal, glial and vascular components, must be examined in an integrated context. Cell–cell signaling and coupling between these different compartments form the basis for normal function. Disordered signaling and perturbed coupling form the basis for dysfunction and disease. In this mini-review, we will survey four examples of this phenomenon: hemodynamic neurovascular coupling linking blood flow to brain activity; cellular communications that evoke the blood–brain barrier phenotype; parallel systems that underlie both neurogenesis and angiogenesis in the CNS; and finally, the potential exchange of trophic factors that may link neuronal, glial and vascular homeostasis. Special issue in honor of Naren Banik.     

Cell–cell communication in Arabidopsis early embryogenesis

The basic body plan of the adult plant is established during embryogenesis, resulting in the juvenile form of the seedling. Arabidopsis embryogenesis is distinguished by a highly regular pattern of cell divisions. Some of these divisions are asymmetric, generating daughter cells with different fates. However, their subsequent differentiation might still depend on cell–cell communication to be fully accomplished or maintained. In some cases, cell fate specification solely depends on cell–cell communication that in general plays an important role in the generation of positional information within the embryo. Although auxin-dependent signalling has received much attention, other ways of cell–cell communication have also been demonstrated or suggested. This review focuses on aspects of pattern formation and cell–cell communication during Arabidopsis embryogenesis up to the mid-globular stage of development.     

Cell specificity in auxin- and ethylene-induced ‘supergrowth’ in Riella helicophylla

Summary In gemmalings of Riella helicophylla, auxin and ethylene stimulate elongation growth, especially of pillar cells. When the two hormones are supplied simultaneously, the effects are additive, i.e. the result is supergrowth. In the cells of the meristem, elongation is enhanced by auxin, but not by ethylene when given alone. However, these cells also respond with supergrowth to a combined treatment with auxin and ethylene. The antiauxin p-chlorophenoxyisobutyric acid suppresses both the ethylene stimulation of cell growth and the additive supergrowth. The results support the concept that auxin pre-conditions the cells to the ethylene-dependent growth event. We suggest that the response elicited by the specific cell types could be related to differences in their level of endogenous auxin.Abbreviations IAA indole-3-acetic acid - PCIB p-chlorophenoxyisobutyric acid     

“Constructing” the Cell Cycle in 3D

The cycle of duplication and division, known as the cell cycle, is the essential mechanism by which all living organisms reproduce. This activity allows students to develop an understanding of the main events that occur during the typical eukaryotic cell cycle mostly in the process of mitotic phase that divides the duplicated genetic material creating two genetically identical daughter cells.     

18β-Glycyrrhetinic Acid Suppresses Cell Proliferation through Inhibiting Thromboxane Synthase in Non-Small Cell Lung Cancer

18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice. The anti-cancer activity of 18β-GA has been studied in many cancer types, whereas its effects in lung cancer remain largely unknown. We first showed that 18β-GA effectively suppressed cell proliferation and inhibited expression as well as activity of thromboxane synthase (TxAS) in non-small cell lung cancer (NSCLC) cells A549 and NCI-H460. In addition, the administration of 18β-GA did not have any additional inhibitory effect on the decrease of cell proliferation induced by transfection with TxAS small interference RNA (siRNA). Moreover, 18β-GA failed to inhibit cell proliferation in the immortalized human bronchial epithelial cells 16HBE-T and another NSCLC cell line NCI-H23, both of which expressed minimal level of TxAS as compared to A549 and NCI-H460. However, 18β-GA abolished the enhancement of cell proliferation induced by transfection of NCI-H23 with pCMV6-TxAS plasmid. Further study found that the activation of both extracellular signal-regulated kinase (ERK)1/2 and cyclic adenosine monophosphate response element binding protein (CREB) induced by TxAS cDNA transfection could be totally blocked by 18β-GA. Altogether, we have delineated that, through inhibiting TxAS and its initiated ERK/CREB signaling, 18β-GA suppresses NSCLC cell proliferation. Our study has highlighted the significance of 18β-GA with respect to prevention and treatment of NSCLC.     

Cell cycle-specific changes in β-adrenergic receptor concentrations in C6 glioma cells

The concentration of β-adrenergic receptors in synchronized C6 cells is lowest during mitosis and G₁ (1000–2000 receptors/cell). A rapid increase in β-receptor concentration occurs in early S phase to 9000 receptors/cell, followed by a decrease during G₂ to the low concentration found at mitosis. In non-synchronized C6 cell populations, mitotic cells have one-half of the average β-receptor concentration of the population as a whole, confirming the observations made with synchronized cells.