scholarly journals Regulation of Antitumor Immune Responses by Exosomes Derived from Tumor and Immune Cells

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 847
Author(s):  
Andrés Rincón-Riveros ◽  
Liliana Lopez ◽  
E Victoria Villegas ◽  
Josefa Antonia Rodriguez
Keyword(s):  
Lipid Membrane ◽  
Multivesicular Body ◽  
Cell Types ◽  
Late Endosome ◽  
Cancer Development ◽  
Common Mechanism ◽  
Tumor Escape ◽  
Research Findings ◽  
A Cell ◽  
Immunosuppressive Microenvironment

Exosomes are lipid membrane-enclosed vesicles released by all cell types that act at the paracrine or endocrine level to favor cell differentiation, tissue homeostasis, organ remodeling and immune regulation. Their biosynthesis begins with a cell membrane invagination which generates an early endosome that matures to a late endosome. By inward budding of the late endosome membrane, a multivesicular body (MVB) with intraluminal vesicles (ILVs) is generated. The fusion of MVBs with the plasma membrane releases ILVs into the extracellular space as exosomes, ranging in size from 30 to 100 nm in diameter. The bilipid exosome membrane is rich in cholesterol, ceramides and phosphatidylserine and can be loaded with DNA, RNA, microRNAs, proteins and lipids. It has been demonstrated that exosome secretion is a common mechanism used by the tumor to generate an immunosuppressive microenvironment that favors cancer development and progression, allowing tumor escape from immune control. Due to their ability to transport proteins, lipids and nucleic acids from the cell that gave rise to them, exosomes can be used as a source of biomarkers with great potential for clinical applications in diagnostic, prognostic or therapeutic areas. This article will review the latest research findings on exosomes and their contribution to cancer development.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

CD38 as an immunomodulator in cancer

2020 ◽  
Vol 16 (34) ◽  
pp. 2853-2861
Author(s):  
Yanli Li ◽  
Rui Yang ◽  
Limo Chen ◽  
Sufang Wu
Keyword(s):  
Multiple Myeloma ◽  
Cell Activation ◽  
Human Tissues ◽  
Transmembrane Glycoprotein ◽  
Cell Activation Marker ◽  
Research Findings ◽  
A Cell ◽  
And Function ◽  
Human Molecule

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

scholarly journals MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1074
Author(s):  
Giuseppina Divisato ◽  
Silvia Piscitelli ◽  
Mariantonietta Elia ◽  
Emanuela Cascone ◽  
Silvia Parisi
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Development ◽  
Special Focus ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Different Cell Types

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.

scholarly journals EMeth: An EM algorithm for cell type decomposition based on DNA methylation data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hanyu Zhang ◽  
Ruoyi Cai ◽  
James Dai ◽  
Wei Sun
Keyword(s):  
Dna Methylation ◽  
Tumor Cells ◽  
T Regulatory Cells ◽  
Simulated Data ◽  
Cell Types ◽  
Computational Method ◽  
Methylation Data ◽  
Cell Type ◽  
A Cell ◽  
Type Decomposition

AbstractWe introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detecting the CpGs whose DNA methylation are inconsistent with the deconvolution model and reducing their contributions to cell type decomposition. Another novel feature of EMeth is that it allows a cell type with known proportions but unknown reference and estimates its methylation. This is motivated by the case of studying methylation in tumor cells while bulk tumor samples include tumor cells as well as other cell types such as infiltrating immune cells, and tumor cell proportion can be estimated by copy number data. We demonstrate that EMeth delivers more accurate estimates of cell type proportions than several other methods using simulated data and in silico mixtures. Applications in cancer studies show that the proportions of T regulatory cells estimated by DNA methylation have expected associations with mutation load and survival time, while the estimates from gene expression miss such associations.

scholarly journals Adhesive multiplicity in the interaction of embryonic fibroblasts and myoblasts with extracellular matrices.

1984 ◽  
Vol 99 (4) ◽  
pp. 1398-1404 ◽  
Author(s):  
C Decker ◽  
R Greggs ◽  
K Duggan ◽  
J Stubbs ◽  
A Horwitz
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Cardiac Fibroblasts ◽  
Cell Types ◽  
Extracellular Matrices ◽  
Common Denominator ◽  
Cell Matrix ◽  
Skeletal Myoblasts ◽  
A Cell ◽  
Cell Matrix Adhesion

Neff et al. (1982, J. Cell Biol., 95:654-666) have described a monoclonal antibody, CSAT, directed against a cell surface antigen that participates in the adhesion of skeletal muscle to extracellular matrices. We used the same antibody to compare and parse the determinants of adhesion and morphology on myogenic and fibrogenic cells. We report here that the antigen is present on skeletal and cardiac muscle and on tendon, skeletal, dermal, and cardiac fibroblasts; however, its contribution to their morphology and adhesion is different. The antibody produces large alterations in the morphology and adhesion of skeletal myoblasts and tendon fibroblasts; in contrast, its effects on the cardiac fibroblasts are not readily detected. The effects of CSAT on the other cell types, i.e., dermal and skeletal fibroblasts, cardiac muscle, 5-bromodeoxyuridine-treated skeletal muscle, lie between these extremes. The effects of CSAT on the skeletal myoblasts depends on the calcium concentration in the growth medium and on the culture age. We interpret these differential responses to CSAT as revealing differences in the adhesion of the various cells to extracellular matrices. This interpretation is supported by parallel studies using quantitative assays of cell-matrix adhesion. The likely origin of these adhesive differences is the progressive display of different kinds of adhesion-related molecules and their organizational complexes on increasingly adhesive cells. The antigen to which CSAT is directed is present on all of the above cells and thus appears to be a lowest common denominator of their adhesion to extracellular matrices.

microRNA-252 and FoxO repress inflammaging by a dual inhibitory mechanism on Dawdle mediated TGF-β pathway in Drosophila

Genetics ◽  
2021 ◽  
Author(s):  
Xiaofen Wu ◽  
Kongyan Niu ◽  
Xiaofan Wang ◽  
Jing Zhao ◽  
Han Wang ◽  
...  
Keyword(s):  
Cell Types ◽  
Innate Immune ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Immune Genes ◽  
Healthy Longevity ◽  
Muscle Tissues ◽  
Distinct Cell ◽  
A Cell ◽  
Innate Immune Genes

Abstract Inflammaging refers to low-grade, chronically activated innate immunity that has deleterious effects on healthy lifespan. However, little is known about the intrinsic signaling pathway that elicits innate immune genes during aging. Here using Drosophila melanogaster, we profile the microRNA targetomes in young and aged animals, and reveal Dawdle (Daw), an activin-like ligand of the TGF-β pathway, as a physiological target of microRNA-252 (miR-252). We show that miR-252 cooperates with Forkhead box O (FoxO), a conserved transcriptional factor implicated in aging, to repress Daw. Unopposed Daw triggers hyper activation of innate immune genes coupled with a decline in organismal survival. Using adult muscle tissues, single-cell sequencing analysis describes that Daw and its downstream innate immune genes are expressed in distinct cell types, suggesting a cell non-autonomous mode of regulation. We further determine the genetic cascade by which Daw signaling leads to increased Kenny/IKKγ protein, which in turn activates Relish/NF-κB protein and consequentially innate immune genes. Finally, transgenic increase of miR-252 and FoxO pathway factors in wild-type Drosophila extends lifespan and mitigates the induction of innate immune genes in aging. Together, we propose that miR-252 and FoxO promote healthy longevity by cooperative inhibition on Daw mediated inflammaging.

Analyses of cellular multimerin 1 receptors: in vitro evidence of binding mediated by αΙΙbβ3 and αvβ3

2005 ◽  
Vol 94 (11) ◽  
pp. 1004-1011 ◽  
Author(s):  
Frédéric Adam ◽  
Shilun Zheng ◽  
Nilesh Joshi ◽  
David Kelton ◽  
Amin Sandhu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Types ◽  
Factor V ◽  
Cellular Activation ◽  
Fiber Assembly ◽  
Expression Studies ◽  
Additional Cell ◽  
A Cell ◽  
Rgd Site

SummaryMultimerin 1 (MMRN1) is a large, soluble, polymeric, factor V binding protein and member of the EMILIN protein family.In vivo, MMRN1 is found in platelets, megakaryocytes, endothelium and extracellular matrix fibers, but not in plasma. To address the mechanism of MMRN1 binding to activated platelets and endothelial cells, we investigated the identity of the major MMRN1 receptors on these cells using wild-type and RGE-forms of recombinant MMRN1. Ligand capture, cell adhesion, ELISA and flow cytometry analyses of platelet-MMRN1 binding, indicated that MMRN1 binds to integrins αIIbβ3 and αvβ3. Endothelial cell binding to MMRN1 was predominantly mediated by αvβ3 and did not require the MMRN1 RGD site or cellular activation. Like many other αvβ3 ligands, MMRN1 had the ability to support adhesion of additional cell types, including stimulated neutrophils. Expression studies, using a cell line capable of endothelial-like MMRN1 processing, indicated that MMRN1 adhesion to cellular receptors enhanced its extracellular matrix fiber assembly. These studies implicate integrin-mediated binding in MMRN1 attachment to cells and indicate that MMRN1 is a ligand for αIIbβ3 and αvβ3.

scholarly journals Cloning and functional characterization of the human fractalkine receptor promoter regions

2002 ◽  
Vol 368 (3) ◽  
pp. 753-760 ◽  
Author(s):  
Alexandre GARIN ◽  
Philippe PELLET ◽  
Philippe DETERRE ◽  
Patrice DEBRÉ ◽  
Christophe COMBADIÈRE
Keyword(s):  
Functional Characterization ◽  
Cell Types ◽  
Promoter Regions ◽  
Exon 2 ◽  
Reading Frame ◽  
Fractalkine Receptor ◽  
A Cell ◽  
Exon 4 ◽  
Coronary Events

We have previously shown that reduced expression of the fractalkine receptor, CX3CR1, is correlated with rapid HIV disease progression and with reduced susceptibility to acute coronary events. In order to elucidate the mechanisms underlying transcriptional regulation of CX3CR1 expression, we structurally and functionally characterized the CX3CR1 gene. It consists of four exons and three introns spanning over 18kb. Three transcripts are produced by splicing the three untranslated exons with exon 4, which contains the complete open reading frame. The transcript predominantly found in leucocytes corresponds to the splicing of exon 2 with exon 4. Transcripts corresponding to splicing of exons 1 and 4 are less abundant in leucocytes and splicing of exons 3 and 4 are rare longer transcripts. A constitutive promoter activity was found in the regions extending upstream from untranslated exons 1 and 2. Interestingly, exons 1 and 2 enhanced the activity of their respective promoters in a cell-specific manner. These data show that the CX3CR1 gene is controlled by three distinct promoter regions, which are regulated by their respective untranslated exons and that lead to the transcription of three mature messengers. This highly complex regulation may allow versatile and precise expression of CX3CR1 in various cell types.

scholarly journals A collection of genetic mouse lines and related tools for inducible and reversible intersectional misexpression

2019 ◽  
Author(s):  
Elham Ahmadzadeh ◽  
N. Sumru Bayin ◽  
Xinli Qu ◽  
Aditi Singh ◽  
Linda Madisen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Genetic Manipulation ◽  
Cell Types ◽  
Biological Processes ◽  
Control Of Gene Expression ◽  
A Cell ◽  
Summary Statement ◽  
Spatiotemporal Control ◽  
Mouse Lines

AbstractThanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches utilizing two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach utilizes available lines expressing tTA/rTA to control timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf) and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms.Summary statementAhmadzadeh et al. present a collection of four mouse lines and genetic tools for misexpression-mediated manipulation of cellular activity with high spatiotemporal control, in a reversible manner.

scholarly journals Epigenetic mechanisms mediating cell state transitions in chondrocytes

2020 ◽  
Author(s):  
Manuela Wuelling ◽  
Christoph Neu ◽  
Andrea M. Thiesen ◽  
Simo Kitanovski ◽  
Yingying Cao ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Cell Lineage ◽  
Cell Types ◽  
State Transitions ◽  
Epigenetic Mechanisms ◽  
Cell Type ◽  
Transition Analysis ◽  
Lineage Differentiation ◽  
A Cell ◽  
Cell Type Specific

AbstractEpigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy.Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with a shift from low to high H3K27ac decoration. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, while HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions.

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