Types Of Cell-cell Interactions Research Articles

Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating.

Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate.

Mutant Huntingtin in Glial Cells Exacerbates Neurological Symptoms of Huntington Disease Mice

Huntington disease (HD) is caused by an expansion of the polyglutamine (polyQ) repeat (>37Q) in huntingtin (htt), and age of onset is inversely correlated with the length of the polyQ repeat. Mutant htt with expanded polyQ is ubiquitously expressed in various types of cells, including glia, but causes selective neurodegeneration. Our recent study demonstrated that expression of the N-terminal mutant htt with a large polyQ repeat (160Q) in astrocytes is sufficient to induce neurological symptoms in mice (Bradford, J., Shin, J. Y., Roberts, M., Wang, C. E., Li, X.-J., and Li, S. H. (2009) Proc. Natl. Acad. Sci. U.S.A. 106, 22480-22485). Because glia-neuron interactions are critical for maintaining the normal function and survival of neurons in the brain and because mutant htt is more abundant in neurons than in glial cells, it is important to investigate whether glial htt can still contribute to HD pathology when mutant htt is abundantly expressed in neuronal cells. We generated transgenic mice that express mutant htt with 98Q in astrocytes. Unlike our recently generated htt-160Q transgenic mice, htt-98Q mice do not show obvious neurological phenotypes, suggesting that the length of the polyQ repeat determines the severity of glial dysfunction. However, htt-98Q mice show increased susceptibility to glutamate-induced seizure. Mice expressing mutant htt in astrocytes were mated with N171-82Q mice that express mutant htt primarily in neuronal cells. Double transgenic mice expressing mutant htt in both neuronal and glial cells display more severe neurological symptoms and earlier death than N171-82Q mice. These findings indicate a role of glial mutant htt in exacerbating HD neuropathology and underscore the importance of improving glial function in treating HD.

Transendothelial Migration of Melanoma Cells Involves N-Cadherin-mediated Adhesion and Activation of the β-Catenin Signaling Pathway

Cancer metastasis is a multistep process involving many types of cell-cell interactions, but little is known about the adhesive interactions and signaling events during extravasation of cancer cells. Transendothelial migration of cancer cells was investigated using an in vitro assay, in which melanoma cells were seeded on top of a monolayer of endothelial cells. Attachment of melanoma cells on the endothelium induced a twofold increase in N-cadherin expression in melanoma cells and the redistribution of N-cadherin to the heterotypic contacts. Transendothelial migration was inhibited when N-cadherin expression was repressed by antisense RNA, indicating a key role played by N-cadherin. Whereas N-cadherin and beta-catenin colocalized in the contact regions between melanoma cells and endothelial cells during the initial stages of attachment, beta-catenin disappeared from the heterotypic contacts during transmigration of melanoma cells. Immunolocalization and immunoprecipitation studies indicate that N-cadherin became tyrosine-phosphorylated, resulting in the dissociation of beta-catenin from these contact regions. Concomitantly, an increase in the nuclear level of beta-catenin occurred in melanoma cells, together with a sixfold increase in beta-catenin-dependent transcription. Transendothelial migration was compromised in cells expressing a dominant-negative form of beta-catenin, thus supporting a regulatory role of beta-catenin signaling in this process.

Isolation and characterization of sea urchin egg lipid rafts and their possible function during fertilization.

Specialized membrane microdomains called rafts are thought to play a role in many types of cell-cell interactions and signaling. We have investigated the possibility that sea urchin eggs contain these specialized membrane microdomains and if they play a role in signal transduction at fertilization. A low density, TX-100 insoluble membrane fraction, typical of lipid rafts, was isolated by equilibrium gradient centrifugation. This raft fraction contained proteins distinct from cytoskeletal complexes. The fraction was enriched in tyrosine phosphorylated proteins and contained two proteins known to be involved in signaling during egg activation (an egg Src-type kinase and PLC gamma). This fraction was further characterized as a prototypical raft fraction by the release of proteins in response to in vitro treatment of the rafts with the cholesterol binding drug, methyl-beta-cyclodextrin (M beta CD). Furthermore, treatment of eggs with M beta CD inhibited fertilization, suggesting that egg lipid rafts play a physiological role in fertilization. Mol. Reprod. Dev. 59:294-305, 2001.

Mouse Sperm Association During Epididymal Transit

Abstract Head-to-head sperm association was described in some species as a normal phenomenon during epididyma transit (Phillips and Bedford, 1987). Recently, a new sperm head association (SHA) was characterized in the rat (Fornés & Burgos 1990; 1994). At this moment, the study of SHA was extended to mouse sperm. SHA is a type of cell-cell interaction clearly observed when an a drop of epididymal fluid, obtained by a puncture of epididymal duct, is placed in a culture medium (HMB media: Modified Ringers medium). This preparation can be observed under contrast phase microscope (optiphot-2, Nikkon) with or without fixative (2% paraformaldehyde and 2% glutaraldehyde in 0.01 M PBS buffer, pH 7,2). The mass of spermatozoa begin to move but not as a single sperm. They move as a clump of sperm and without fixative the sperm motility alone disaggregate the SHA.

Early patterning of the C. elegans embryo.

Studies of about 20 maternally expressed genes are providing an understanding of mechanisms of patterning and cell-fate determination in the early Caenorhabditis elegans embryo. The analyses have revealed that fates of the early blastomeres are specified by a combination of intrinsically asymmetric cell divisions and two types of cell-cell interactions: inductions and polarizing interactions. In this review we summarize the current level of understanding of the molecular mechanisms underlying these processes in the specification of cell fates in the pregastrulation embryo.

Development of Osteoclasts From Embryonic Stem Cells Through a Pathway That Is c-fms but not c-kit Dependent

AbstractOsteoclasts are hematopoietic cells essential for bone resorption. To study the derivation of these interesting cells, we developed a stepwise culture system where stromal cells promote embryonic stem (ES) cells to differentiate into mature osteoclasts. Three phases to this differentiation process include (1) induction of hematopoiesis, along with the generation of osteoclast precursors, (2) expansion of these precursors, and (3) terminal differentiation into mature osteoclasts in the presence of 1α,25-dihydroxyvitamine D3 . Although the transition of ES cells to the hematopoietic lineage was not blocked by an antibody to c-fms, later phases were dependent on a signaling through this transmembrane receptor as indicated by the finding that anti–c-fms treatment of cells in the second and third phases reduced the number of osteoclasts produced by 75% and more than 99%, respectively. Blockade of signaling through another tyrosine kinase–type receptor, c-kit, did not affect any stages of osteoclastogenesis, although generation of other hemopoietic lineages was reduced to less than 10% of untreated. When small numbers of ES cells were directly cultured under conditions that promote osteoclast differentiation, tartrate-resistant acid phosphatase-positive multinucleated cells were observed at the edge but not inside of colonies. This suggests that some types of cell-cell interactions may inhibit development of mature osteoclasts. The culture system developed here provides an important tool for osteoclast biology.

Regulation of ovarian follicular development in primates: facts and hypotheses.

IN THE adult ovary, folliculogenesis starts when follicles leave the pool of resting follicles (RF) to enter the growth phase. From there, the early growing follicle undergoes a developmental process including a dramatic course of cellular proliferation and differentiation. In primates, only one follicle commonly reaches the preovulatory stage every cycle; most follicles fail to complete this maturation scheme, dying in the process termed atresia. In recent years, a picture has emerged depicting the classic endocrine control of ovarian function by LH and FSH, entangled in a maze of regulatory systems hinging on cell-cell interactions between follicular cells, via action of a variety of molecules (1–3). Different types of cell-cell interactions have been described. In paracrine regulations, a molecule synthesized by one cellular type is released into the interstitial milieu to act directly on another cellular type. In autocrine regulations, molecules synthesized by one cellular type are released to act either on the same tissue (autocrine action), on immediate neighbor cells (juxtacrine action), or are not released and act inside the producing cell itself (intracrine action). These paracrine and autocrine regulations may be involved at every stage of folliculogenesis by acting either alone or by modifying the multiple functions of FSH and LH. Finally, it appears from these findings that during folliculogenesis a finely tuned process of progressive differentiation occurs in all constituents of the follicle.