scholarly journals Myoepithelial cells are a dynamic barrier to epithelial dissemination

2018 ◽  
Vol 217 (10) ◽  
pp. 3368-3381 ◽  
Author(s):  
Orit Katarina Sirka ◽  
Eliah R. Shamir ◽  
Andrew J. Ewald
Keyword(s):  
Smooth Muscle ◽  
Cancer Cells ◽  
Barrier Function ◽  
Myoepithelial Cell ◽  
Smooth Muscle Actin ◽  
Myoepithelial Cells ◽  
Escape Time ◽  
Specific Expression ◽  
Twist1 Expression

The mammary epithelium is composed of an inner luminal and surrounding myoepithelial cell layer. The presence of cancer cells beyond the myoepithelium defines invasive breast cancer, yet the role of the myoepithelium during invasion remains unclear. We developed a 3D organotypic culture assay to model this process through lineage-specific expression of the prometastatic transcription factor Twist1. We sought to distinguish the functional role of the myoepithelium in regulating invasion and local dissemination. Myoepithelial-specific Twist1 expression induced cell-autonomous myoepithelial cell escape. Remarkably, luminal-specific Twist1 expression was rarely sufficient for escape. Time-lapse microscopy revealed that myoepithelial cells collectively restrain and reinternalize invading Twist1+ luminal cells. Barrier function correlated with myoepithelial abundance and required the expression of α-smooth muscle actin and P-cadherin. We next demonstrated that myoepithelial cells can restrain and recapture invasive cancer cells. Our data establish the concept of the myoepithelium as a dynamic barrier to luminal dissemination and implicate both smooth muscle contractility and intercellular adhesion in barrier function.

scholarly journals Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Qian Cheng ◽  
Xin Li ◽  
Jingru Liu ◽  
Qinmao Ye ◽  
Yanfang Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Cancer Cells ◽  
Smooth Muscle Actin ◽  
Muscle Actin ◽  
Cancer Associated Fibroblast ◽  
Secretion Inhibition

Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs) via conveying microRNAs (miRs). miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6) secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM) cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line) exosomes (OPM2-exo) on regulating the proliferation, cancer-associated fibroblast (CAF) transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP), α-smooth muscle actin (α-SMA), and stromal-derived factor 1 (SDF-1) expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

scholarly journals Jagged1/Notch3 Signaling Modulates Hemangioma-Derived Pericyte Proliferation and Maturation

2016 ◽  
Vol 40 (5) ◽  
pp. 895-907 ◽  
Author(s):  
Yi Ji ◽  
Siyuan Chen ◽  
Bo Xiang ◽  
Yuan Li ◽  
Li Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Growth Arrest ◽  
Notch Signaling Pathway ◽  
Cell Growth Arrest ◽  
Muscle Myosin ◽  
Dependent Mechanism

Background: The Notch signaling pathway has been implicated in the pericyte phenotype, but its exact roles in hemangioma-derived pericytes (Hem-pericytes) remain ill defined. Methods: Hem-pericytes were stimulated by immobilized recombinant Jagged1. The potential mechanisms of Notch-induced Hem-pericytes growth arrest were investigated by cell cycle assay, and the role of the Notch in promoting Hem-pericyte maturation was also analyzed by real-time PCR and western blot. Results: Activation of Notch3 in Hem-pericytes significantly reduced cell proliferation and inhibited cell cycle transition. This event was associated with an increase in the levels of p21Cip1. Knockdown of p21Cip1 resulted in a significant rescue of Notch-induced cell growth arrest and an entry into the cell cycle. We showed that Jagged1 activation of Notch3 signaling upregulated the expression of the pericyte contractile markers smooth muscle myosin heavy chain (smMHC) and α-smooth muscle actin (αSMA), concomitant with an increase in the expression of myocardin in Hem-pericytes. We further revealed that the endothelial-derived Jagged1 modulated the Hem-pericyte phenotype via a contact-dependent mechanism. Conclusions: Our results demonstrated that Jagged1 activation of Notch3 resulted in a significant decrease in cell proliferation while concomitantly promoting Hem-pericyte maturation. These data provide initial evidence that Notch induces a quiescent phenotype in Hem-pericytes.

scholarly journals HDAC8 inhibition ameliorates pulmonary fibrosis

2019 ◽  
Vol 316 (1) ◽  
pp. L175-L186 ◽  
Author(s):  
Shigeki Saito ◽  
Yan Zhuang ◽  
Takayoshi Suzuki ◽  
Yosuke Ota ◽  
Marjorie E. Bateman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Smooth Muscle Actin ◽  
Lung Fibroblasts ◽  
Peroxisome Proliferator ◽  
Collagen Gels ◽  
Cell Contractility

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease, and fibroblast-myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase-8 (HDAC8) has been shown to associate with α-smooth muscle actin (α-SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been reported. This study investigated the role of HDAC8 in pulmonary fibrosis with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as transforming growth factor (TGF)β1-treated normal human lung fibroblasts (NHLFs). Immunoprecipitation experiments revealed that HDAC8 was associated with α-SMA in TGFβ1-treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8-selective inhibitor) repressed TGFβ1-induced fibroblast contraction and α-SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGFβ1-induced expression of profibrotic molecules such as fibronectin and increased expression of antifibrotic molecules such as peroxisome proliferator-activated receptor-γ (PPARγ). Chromatin immunoprecipitation quantitative PCR using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGFβ1-induced loss of H3K27ac at the PPARγ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as expression of type 1 collagen and fibronectin in bleomycin-treated mouse lungs. These data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases.

Role of Alpha-Smooth Muscle Actin and Fibroblast Activation Protein Alpha in Ovarian Neoplasms

2018 ◽  
Vol 83 (4) ◽  
pp. 381-387 ◽  
Author(s):  
Ana Carolinne da Silva ◽  
Millena Prata Jammal ◽  
Renata Margarida Etchebehere ◽  
Eddie Fernando Candido Murta ◽  
Rosekeila Simões Nomelini
Keyword(s):  
Smooth Muscle ◽  
Ovarian Neoplasms ◽  
Smooth Muscle Actin ◽  
Fibroblast Activation Protein ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Fibroblast Activation ◽  
Fibroblast Activation Protein Alpha

scholarly journals Morphology of the Myoepithelial Cell: Immunohistochemical Characterization from Resting to Motile Phase

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Germana Beha ◽  
Giuseppe Sarli ◽  
Barbara Brunetti ◽  
Francesco Sassi ◽  
Domenico Ferrara ◽  
...  
Keyword(s):  
Myoepithelial Cell ◽  
Smooth Muscle Actin ◽  
Myoepithelial Cells ◽  
Biological Behavior ◽  
Cytokeratin 19 ◽  
Mesenchymal Phenotype ◽  
Cytokeratin 5 ◽  
Cytokeratin 14 ◽  
Mixed Tumors

Myoepithelium is present in canine mammary tumors as resting and proliferative suprabasal and spindle and stellate interstitial cells. The aim of this paper was to evaluate a panel of markers for the identification of four different myoepithelial cell morphological types in the normal and neoplastic mammary gland and to investigate immunohistochemical changes from an epithelial to a mesenchymal phenotype. Cytokeratin 19 (CK19), cytokeratin 5/6 (CK5/6), cytokeratin 14 (CK14), estrogen receptor (ER), p63 protein, vimentin (VIM), andα-smooth muscle actin (Alpha-SMA) antibodies were used on 29 neoplasms (3 benign and 3 malignant myoepithelial tumors, 7 carcinomas in benign-mixed tumors and 16 complex carcinomas) and on normal tissue of mammary glands. All these antibodies were also tested on 3 mammary tissues from animals with no mammary pathology. The myoepithelial markers were well expressed in the suprabasal cells and gradually lost in the motile types, with the stellate cells maintaining only VIM expression typical of mesenchyma. ER labeled some resting and motile myoepithelial cells. On the basis of our results, we propose a transition from myoepithelial immotile cells into migratory fibroblast-like cells. This transition and the characterization of an immunohistochemical panel for resting and motile myoepithelial cells shed more light on the biological behavior of myoepithelial cells.

scholarly journals Requirement of a Myocardin-Related Transcription Factor for Development of Mammary Myoepithelial Cells

2006 ◽  
Vol 26 (15) ◽  
pp. 5797-5808 ◽  
Author(s):  
Shijie Li ◽  
Shurong Chang ◽  
Xiaoxia Qi ◽  
James A. Richardson ◽  
Eric N. Olson
Keyword(s):  
Transcription Factor ◽  
Smooth Muscle ◽  
Myoepithelial Cell ◽  
Serum Response Factor ◽  
Cell Lineage ◽  
Myoepithelial Cells ◽  
Embryonic Cell ◽  
Loss Of Function ◽  
Muscle Gene Expression ◽  
Related Transcription Factor

ABSTRACT The mammary gland consists of a branched ductal system comprised of milk-producing epithelial cells that form ductile tubules surrounded by a myoepithelial cell layer that provides contractility required for milk ejection. Myoepithelial cells bear a striking resemblance to smooth muscle cells, but they are derived from a different embryonic cell lineage, and little is known of the mechanisms that control their differentiation. Members of the myocardin family of transcriptional coactivators cooperate with serum response factor to activate smooth muscle gene expression. We show that female mice homozygous for a loss-of-function mutation of the myocardin-related transcription factor A (MRTF-A) gene are unable to effectively nurse their offspring due to a failure in maintenance of the differentiated state of mammary myoepithelial cells during lactation, resulting in apoptosis of this cell population, a consequent inability to release milk, and premature involution. The phenotype of MRTF-A mutant mice reveals a specific and essential role for MRTF-A in mammary myoepithelial cell differentiation and points to commonalities in the transcriptional mechanisms that control differentiation of smooth muscle and myoepithelial cells.

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