DOCSLIB.ORG

The Matrix Revolution: Matricellular Proteins and Restructuring of The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Matrix Revolution: Matricellular Proteins and Restructuring of The Author Manuscript Published OnlineFirst on March 19, 2020; DOI: 10.1158/0008-5472.CAN-18-2098 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 The Matrix Revolution: Matricellular Proteins and Restructuring of the 2 Cancer Microenvironment 3 4 Casimiro Gerarduzzi1,2,*,#, Ursula Hartmann3, Andrew Leask4 and Elliot Drobetsky1,2 5 6 7 1Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, Québec H1T 2M4, Canada 8 2Département de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada 9 3Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany 10 4College of Dentistry, University of Saskatchewan, 105 Wiggins Rd, Saskatoon SK S7N 5E4, Canada 11 12 13 *To whom correspondence should be addressed: Casimiro Gerarduzzi, PhD, Maisonneuve-Rosemont 14 Hospital Research Center, Division of Nephrology, 5415, boul. de l'Assomption, Montreal, Quebec, 15 Canada, H1T 2M4. Phone: (514) 252-3400 ext.2813, email: [email protected] 16 #Senior Author 17 18 19 Running title: The Role of Matricellular Proteins in Cancer 20 Keywords: Matricellular Proteins, Extracellular Matrix, Microenvironment, Cancer Progression, 21 Biomarkers/Therapeutics 22 Number of Figures: 1 23 Conflict of interest: The authors declare no potential conflicts of interest. 1 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on March 19, 2020; DOI: 10.1158/0008-5472.CAN-18-2098 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 24 25 Abstract 26 The extracellular matrix (ECM) surrounding cells is indispensable for regulating their 27 behavior. The dynamics of ECM signaling are tightly controlled throughout growth and 28 development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the 29 ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins 30 and cell-matrix interactions to influence normal cellular functions. In the tumor 31 microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can 32 support multiple hallmarks of carcinogenesis by interacting with various cellular components 33 that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the 34 biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This 35 realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, 36 as well as effective and selective therapeutic targets. 37 2 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on March 19, 2020; DOI: 10.1158/0008-5472.CAN-18-2098 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 38 Introduction 39 The behavior of individual cells is influenced by a plethora of signals originating from the 40 surrounding microenvironment, which includes the extracellular matrix (ECM). Previously 41 regarded as merely a static scaffold for cell/tissue organization, the ECM is now viewed as a 42 critical niche contributing to the regulation of cellular survival, proliferation and migration. This 43 realization has positioned the ECM at the center stage of normal physiological processes such 44 as development, tissue homeostasis and tissue remodeling. 45 The dynamic nature of ECM signaling is determined by a secreted subset of non- 46 structural matricellular proteins (MCPs) (1), in contrast to the structural roles of “classical” ECM 47 proteins such as collagen and fibronectin (2). MCP functional versatility is achieved by its 48 multiple domains that either (i) bind ECM proteins and/or cell surface receptors, (ii) bind and 49 regulate the activity or accessibility of extracellular signaling molecules such as growth factors, 50 proteases, chemokines, and cytokines, or (iii) mediate intrinsic enzymatic activities to precisely 51 orchestrate the assembly, degradation, and organization of the ECM. MCPs are tightly 52 controlled, with expression promptly occurring in context-specific scenarios. Typically, they are 53 highly expressed during early development, ultimately subsiding in adult tissues under 54 physiological conditions. However, transient re-expression is observed during injury repair, and 55 can also be sustained in chronic pathologies such as cancer (2-7). Indeed, chronic unscheduled 56 expression of various MCPs, either by tumor cells or the surrounding stroma (8), leads to 57 abnormal ECM remodeling and stimulation of mitogenic pathways essential for cancer 58 progression. This may underlie the correlation between the upregulation of many MCPs and 3 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on March 19, 2020; DOI: 10.1158/0008-5472.CAN-18-2098 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 59 poor prognosis in cancer patients (9) and, moreover, provide rationale for exploring the utility 60 of MCPs as cancer biomarkers and therapeutic targets. 61 This review will focus on the burgeoning roles of the MCP families SPARC, CCN, SIBLING, 62 Tenascin and Gla-containing proteins in both cancer development, detection and treatment. 63 Certainly, members of these particular families are aberrantly expressed in various tumor types, 64 and moreover exhibit biochemical, biomechanical and metastatic properties influencing cancer 65 progression. 66 67 Normal physiological roles of MCPs 68 The ever-growing number of newly-discovered MCPs has necessitated their 69 classification into families. Members are grouped based on shared domains, which in turn 70 reflect the functional diversity between families. 71 The SPARC protein (Secreted Protein Acidic and Rich in Cysteine; hereafter alternative 72 protein names are included in parentheses; BM40, osteonectin), one of the original MCPs to be 73 characterized, is considered prototypical due to its simple structure and rich functionality. The 74 subsequent discovery of other MCPs with structural similarity revealed a broader family of 75 SPARC-related proteins (10). Such SPARC family members share follistatin-like and extracellular 76 calcium-binding (EC) domains, and are classified into five distinct groups based on sequence 77 homology of their EC domains (10): SPARCs, SPARCL1, SMOCs, SPOCKs and Follistatin-like 78 protein-1 (FSTL1). SPARC family members were shown to regulate ECM assembly and 79 deposition, influence cytokine activity, inhibit cell adhesion and cell cycle progression, regulate 80 cell differentiation and activate matrix metalloproteinases (10). While most SPARC members 4 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on March 19, 2020; DOI: 10.1158/0008-5472.CAN-18-2098 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 81 exhibit ubiquitous expression throughout early development, in adults, expression is largely 82 limited to tissues that are diseased or undergoing wound repair/remodeling. 83 The vertebrate CCN (Centralized Coordination Network) family is composed of six 84 homologous cysteine-rich members (11): CCN1 (CYR61), CCN2 (CTGF), CCN3 (NOV), CCN4 85 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3). Each is comprised of an N-terminal secretory 86 peptide and four functional domains: insulin-like growth factor-binding protein domain (IGFBP), 87 Von Willebrand factor domain (VWR), thrombospondin type-1 repeat module (TSR) and 88 carboxy-terminal cysteine-knot (CT) motif (11). In response to tissue remodeling, CCN proteins 89 are expressed, principally in mesenchymal cells, during development and in connective tissue 90 pathologies (12). The postnatal role of CCN proteins is known for promoting collagen stability or 91 organization (13). 92 Tenascins (TNs) comprise a family of four large extracellular matrix glycoproteins, i.e., 93 TN-C, -R, -W and -X, which exist as either trimers or hexamers (14). TNs share a characteristic 94 modular structure composed of tandem epidermal growth factor (EGF)-like domains, 95 fibronectin-type III domains and a C-terminal fibrinogen related domain (FReD). Consequently, 96 TNs share functions in modulating cellular responses to the ECM and growth factors, specifically 97 regulating growth, differentiation, adhesion and migration during tissue remodeling events 98 (15). However, each member has distinct spatial and temporal expression. TN-C expression is 99 typically present in all organs during fetal development and mechanical stress, whereas TN-W 100 expression is restricted to developing/remodeling bone and certain stem cell niches (14). TN-R 101 is expressed exclusively in the developing and adult nervous system, while TN-X represents a 5 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on March 19, 2020; DOI: 10.1158/0008-5472.CAN-18-2098 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 102 constitutive ECM component of most connective tissues, being hardly influenced by external 103 factors (14). 104 The SIBLING (Small Integrin-Binding
Load more

Recommended publications
  • Global Analysis Reveals the Complexity of the Human Glomerular Extracellular Matrix
    Global analysis reveals the complexity of the human glomerular extracellular matrix Rachel Lennon,1,2 Adam Byron,1,* Jonathan D. Humphries,1 Michael J. Randles,1,2 Alex Carisey,1 Stephanie Murphy,1,2 David Knight,3 Paul E. Brenchley,2 Roy Zent,4,5 and Martin J. Humphries.1 1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK; 2Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; 3Biological Mass Spectrometry Core Facility, Faculty of Life Sciences, University of Manchester, Manchester, UK; 4Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; and 5Veterans Affairs Hospital, Nashville, TN, USA. *Present address: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. Running title: Proteome of the glomerular matrix Word count: Abstract: 208, main text 2765 Corresponding author: Dr Rachel Lennon, Wellcome Trust Centre for Cell-Matrix Research, Michael Smith Building, University of Manchester, Manchester M13 9PT, UK. Phone: 0044 (0) 161 2755498. Fax: 0044 (0) 161 2755082. Email: [email protected] Abstract The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. Here, we employed mass spectrometry–based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalogue includes all previously identified glomerular components, plus many new and abundant components.
    [Show full text]
  • Immunohistochemical Expression of Tenascin and Elastin In
    Clinical Obstetrics, Gynecology and Reproductive Medicine Research Article ISSN: 2059-4828 Immunohistochemical expression of tenascin and elastin in women with pelvic organ prolapse and/or without stress urinary incontinence Ilias Liapis1, Panagiotis Bakas2, Pafiti-Kondi Agatha3, Matrona Frangou-Plemenou4, Charalampos Karachalios5*, Dimos Sioutis6 and Aggelos Liapis2 1Birmingham Women’s and Children’s Hospital, NHS Foundation Trust, Health Education England Midlands and East-West Midlands, Birmingham, England, United Kingdom 2Second Department of Obstetrics and Gynecology, Aretaieio University Hospital, School of Health Sciences, Medical School, National and Kapodistrian University of Athens, Athens, Attica, Greece 3Pathology Laboratory, Aretaieio University Hospital, School of Health Sciences, Medical School, National and Kapodistrian University of Athens, Athens, Attica, Greece 4Microbiology Laboratory, Aretaieio University Hospital, School of Health Sciences, Medical School, National and Kapodistrian University of Athens, Athens, Attica, Greece 5Second Department of Obstetrics and Gynecology, Aretaieio University Hospital, School of Health Sciences, Medical School, National and Kapodistrian University of Athens, Athens, Attica, Greece 6Third Department of Obstetrics and Gynecology, Attikon University Hospital, School of Health Sciences, Medical School, National and Kapodistrian University of Athens, Athens, Attica, Greece Abstract Background and aim: Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) constitute entities of pelvic floor disorders and most often occur simultaneously in the same patient, adversely affecting women’s quality of life. The pathogenesis of pelvic organ prolapse and stress urinary incontinence is not fully understood. The pelvic viscera are maintained in their place thanks to interconnection of levator ani muscles, cardinal and uterosacral ligaments, and pubocervical and rectovaginal fascia. Ligaments and fascia consist mainly of connective tissue.
    [Show full text]
  • Human Periprostatic Adipose Tissue: Secretome from Patients With
    CANCER GENOMICS & PROTEOMICS 16 : 29-58 (2019) doi:10.21873/cgp.20110 Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia PAULA ALEJANDRA SACCA 1, OSVALDO NÉSTOR MAZZA 2, CARLOS SCORTICATI 2, GONZALO VITAGLIANO 3, GABRIEL CASAS 4 and JUAN CARLOS CALVO 1,5 1Institute of Biology and Experimental Medicine (IBYME), CONICET, Buenos Aires, Argentina; 2Department of Urology, School of Medicine, University of Buenos Aires, Clínical Hospital “José de San Martín”, Buenos Aires, Argentina; 3Department of Urology, Deutsches Hospital, Buenos Aires, Argentina; 4Department of Pathology, Deutsches Hospital, Buenos Aires, Argentina; 5Department of Biological Chemistry, School of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina Abstract. Background/Aim: Periprostatic adipose tissue Prostate cancer (PCa) is the second most common cancer in (PPAT) directs tumour behaviour. Microenvironment secretome men worldwide. While most men have indolent disease, provides information related to its biology. This study was which can be treated properly, the problem consists in performed to identify secreted proteins by PPAT, from both reliably distinguishing between indolent and aggressive prostate cancer and benign prostate hyperplasia (BPH) disease. Evidence shows that the microenvironment affects patients. Patients and Methods: Liquid chromatography-mass tumour behavior. spectrometry-based proteomic analysis was performed in Adipose tissue microenvironment is now known to direct PPAT-conditioned media (CM) from patients with prostate tumour growth, invasion and metastases (1, 2). Adipose cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or tissue is adjacent to the prostate gland and the site of benign disease (CM-BPH). Results: The highest number and invasion of PCa.
    [Show full text]
  • Maturation, Playing Position and Genetic Variation
    MATURATION, PLAYING POSITION AND GENETIC VARIATION: INJURY RISK FACTORS IN HIGH-LEVEL YOUTH SOCCER ELLIOTT C R HALL A thesis submitted in partial fulfilment of the requirements of Liverpool John Moores University for the degree of Doctor of Philosophy September 2019 ACKNOWLEDGEMENTS I wish to thank all those who have helped me in completing this PhD thesis, particularly my supervisory team. It has been a privilege to work with and learn from you all, and I am extremely grateful for the opportunity. I would like to express sincere gratitude to my Director of Studies, Dr. Rob Erskine, firstly for considering me for this PhD, and secondly for the exceptional guidance and support throughout the project. The work ethic, passion and drive you have displayed has motivated me to perform to the best of my ability, and my development has been guided by your valuable knowledge and experience. I hope the faith you displayed in nominating me for this project has been in some way repaid by the work we have achieved. I would like to thank Professor Barry Drust. I feel very fortunate to have had the opportunity to work under your guidance, particularly as this project involves a sport to which you have contributed so much invaluable knowledge and passion. Importantly, you have helped me to see things differently than I did at the start of this journey, and to see the ‘bigger picture’ in academic and personal life. It is also imperative to mention your support during participant recruitment, which contributed significantly to the success of this project.
    [Show full text]
  • The EMILIN/Multimerin Family
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE REVIEW ARTICLE published: 06 Januaryprovided 2012 by Frontiers - Publisher Connector doi: 10.3389/fimmu.2011.00093 The EMILIN/multimerin family Alfonso Colombatti 1,2,3*, Paola Spessotto1, Roberto Doliana1, Maurizio Mongiat 1, Giorgio Maria Bressan4 and Gennaro Esposito2,3 1 Experimental Oncology 2, Centro di Riferimento Oncologico, Istituto di Ricerca e Cura a Carattere Scientifico, Aviano, Italy 2 Department of Biomedical Science and Technology, University of Udine, Udine, Italy 3 Microgravity, Ageing, Training, Immobility Excellence Center, University of Udine, Udine, Italy 4 Department of Histology Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy Edited by: Elastin microfibrillar interface proteins (EMILINs) and Multimerins (EMILIN1, EMILIN2, Uday Kishore, Brunel University, UK Multimerin1, and Multimerin2) constitute a four member family that in addition to the Reviewed by: shared C-terminus gC1q domain typical of the gC1q/TNF superfamily members contain a Uday Kishore, Brunel University, UK Kenneth Reid, Green Templeton N-terminus unique cysteine-rich EMI domain. These glycoproteins are homotrimeric and College University of Oxford, UK assemble into high molecular weight multimers. They are predominantly expressed in *Correspondence: the extracellular matrix and contribute to several cellular functions in part associated with Alfonso Colombatti, Division of the gC1q domain and in part not yet assigned nor linked to other specific regions of the Experimental Oncology 2, Centro di sequence. Among the latter is the control of arterial blood pressure, the inhibition of Bacil- Riferimento Oncologico, Istituto di Ricerca e Cura a Carattere Scientifico, lus anthracis cell cytotoxicity, the promotion of cell death, the proangiogenic function, and 33081 Aviano, Italy.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Matrix Gla Protein Species and Risk of Cardiovascular Events in Type 2 Diabetic Patients
    Cardiovascular and Metabolic Risk ORIGINAL ARTICLE Matrix Gla Protein Species and Risk of Cardiovascular Events in Type 2 Diabetic Patients 1 3 GEERTJE W. DALMEIJER, PHD W.M. MONIQUE VERSCHUREN, PHD reduced coronary artery calcification and 1 3 YVONNE T. VAN DER SCHOUW, PHD JOLANDA M.A. BOER, PHD – 2 1 reduced risk of CVD (6 9). These effects ELKE J. MAGDELEYNS, BSC JOLINE W.J. BEULENS, PHD 2 are thought to be mediated by increased CEES VERMEER, PHD activation of MGP (10). MGP exists as various species, which OBJECTIVEd differ in their state of phosphorylation To investigate the relationship of circulating matrix Gla protein (MGP) species or carboxylation: phosphorylated, non- with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic phosphorylated (desphospho-MGP patients. [dpMGP]), carboxylated (cMGP), or un- RESEARCH DESIGN AND METHODSdEPIC-NL is a prospective cohort study among carboxylated (ucMGP). Total uncarboxy- 40,011 Dutch men and women. At baseline (1993–1997), 518 participants were known to have lated MGP (t-ucMGP) is thought to be type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The the sum of desphospho-uncarboxylated incidence of fatal and nonfatal CVD and CVD subtypesdCHD, peripheral arterial disease (PAD), MGP (dp-ucMGP) and phosphorylated- d heart failure, and stroke were obtained by linkage to national registers. Cox proportional uncarboxylated MGP (p-ucMGP) and hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, mainly consists of p-ucMGP. physical activity, and history of CVD. Development of assays to measure RESULTSdDuring a median 11.2 years of follow-up, 160 cases of CVD were documented.
    [Show full text]
  • Inactive Matrix Gla Protein Is a Novel Circulating Biomarker Predicting
    www.nature.com/scientificreports OPEN Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar Received: 5 June 2018 Accepted: 17 September 2018 narrowing in humans Published: xx xx xxxx Fang-Fei Wei1, Qi-Fang Huang1, Zhen-Yu Zhang1, Karel Van Keer2, Lutgarde Thijs1, Sander Trenson3, Wen-Yi Yang1, Nicholas Cauwenberghs 1, Blerim Mujaj1, Tatiana Kuznetsova1, Karel Allegaert4,5, Harry A. J. Struijker-Boudier6, Peter Verhamme7, Cees Vermeer8 & Jan A. Staessen 1,9 Active matrix Gla protein (MGP), a potent inhibitor of calcifcation in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp–ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996–2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008–2015). CRAE (P = 0.005) and AVR (P = 0.080) at follow-up decreased across tertiles of the dp–ucMGP distribution. In unadjusted models, for a doubling of dp–ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40 µm (95% confdence interval [CI], 0.32 to 2.48; P = 0.011) and 0.006 (CI, 0.001 to 0.011; P = 0.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were −1.03 µm (CI, −1.96 to −0.11; P = 0.028) and −0.007 (CI, −0.011 to −0.002; P = 0.007).
    [Show full text]
  • TSPAN9 and EMILIN1 Synergistically Inhibit the Migration and Invasion Of
    Qi et al. BMC Cancer (2019) 19:630 https://doi.org/10.1186/s12885-019-5810-2 RESEARCHARTICLE Open Access TSPAN9 and EMILIN1 synergistically inhibit the migration and invasion of gastric cancer cells by increasing TSPAN9 expression Yaoyue Qi1, Jing Lv2, Shihai Liu3, Libin Sun2, Yixuan Wang1, Hui Li1, Weiwei Qi2* and Wensheng Qiu2* Abstract Background: Globally, the incidence and mortality rates of gastric cancer are high, and its poor prognosis is closely related to tumor recurrence and metastasis. Therefore, the molecular mechanisms associated with the migration and invasion of gastric cancer cells are important for gastric cancer treatment. Previously, TSPAN9 has been reported to inhibit gastric cancer cell migration; however, the underlying molecular mechanism remains unclear. Methods: Human gastric adenocarcinoma cell lines, SGC7901 and AGS, were cultured in vitro. TSPAN9 expression was determined by RT-PCR, western blot analysis, and immunohistochemistry in gastric cancer and tumor-adjacent tissues. Following the over-expression and knockdown of TSPAN9, wound healing and cell invasion assays were performed and EMT-related protein expression was evaluated to analyze the invasion and migration of gastric cancer cells. TSPAN9 expression and the invasion and metastasis of gastric cancer cells were observed by the functional assays following EMILIN1 over-expression. Results: Inhibiting TSPAN9 expression significantly promoted the migration and invasion of gastric cancer cells. In addition, immunofluorescence co-localization and co-immunoprecipitation analysis revealed closely related expression of EMILIN1 and TSPAN9. Moreover, EMILIN1 can synergistically boost the tumor suppressive effect of TSPAN9, which may be produced by promoting TSPAN9 expression. Conclusions: We have demonstrated that EMILIN1 induces anti-tumor effects by up-regulating TSPAN9 expression in gastric cancer.
    [Show full text]
  • Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis
    International Journal of Molecular Sciences Article Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis Ana Amor López 1, Marina S. Mazariegos 1, Alessandra Capuano 2 , Pilar Ximénez-Embún 3, Marta Hergueta-Redondo 1, Juan Ángel Recio 4 , Eva Muñoz 5,Fátima Al-Shahrour 6 , Javier Muñoz 3, Diego Megías 7, Roberto Doliana 2, Paola Spessotto 2 and Héctor Peinado 1,* 1 Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain; [email protected] (A.A.L.); [email protected] (M.S.M.); [email protected] (M.H.-R.) 2 Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), Department of Advanced Cancer Research and Diagnostics, IRCCS, I-33081 Aviano, Italy; [email protected] (A.C.); [email protected] (R.D.); [email protected] (P.S.) 3 Proteomics Unit—ProteoRed-ISCIII, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; [email protected] (P.X.-E.); [email protected] (J.M.) 4 Biomedical Research in Melanoma-Animal Models and Cancer Laboratory, Vall d’Hebron Research Institute VHIR-Vall d’Hebron Hospital Barcelona-UAB, 08035 Barcelona, Spain; [email protected] 5 Clinical Oncology Program, Vall d’Hebron Institute of Oncology-VHIO, Vall d’Hebron Hospital, Barcelona-UAB, 08035 Barcelona, Spain; [email protected] Citation: Amor López, A.; 6 Bioinformatics Unit, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Mazariegos, M.S.; Capuano, A.; 28029 Madrid, Spain; [email protected] Ximénez-Embún, P.; Hergueta- 7 Confocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Redondo, M.; Recio, J.Á.; Muñoz, E.; 28029 Madrid, Spain; [email protected] Al-Shahrour, F.; Muñoz, J.; Megías, D.; * Correspondence: [email protected] et al.
    [Show full text]
  • Tenascins in Stem Cell Niches
    MATBIO-01031; No of Pages 12 Matrix Biology xxx (2014) xxx–xxx Contents lists available at ScienceDirect Matrix Biology journal homepage: www.elsevier.com/locate/matbio Tenascins in stem cell niches Ruth Chiquet-Ehrismann a,b,⁎,1,GertraudOrendc,d,e,f,1, Matthias Chiquet g,1, Richard P. Tucker h,1, Kim S. Midwood i,1 a Friedrich Miescher Institute of Biomedical Research, Novartis Research Foundation, Maulbeerstrasse 66 CH-4058 Basel, Switzerland b Faculty of Sciences, University of Basel, Switzerland c Inserm U1109, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy (MNT3) Team, 3 av. Molière, 67200 Strasbourg, France d Université de Strasbourg, 67000 Strasbourg, France e LabEx Medalis, Université de Strasbourg, 67000 Strasbourg, France f Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France g Department of Orthodontics and Dentofacial Orthopedics, University of Bern, Freiburgstrasse 7, CH-3010 Bern, Switzerland h Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA 95616, USA i The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7FY, United Kingdom article info abstract Available online xxxx Tenascins are extracellular matrix proteins with distinct spatial and temporal expression during development, tissue homeostasis and disease. Based on their expression patterns and knockout phenotypes an important Keywords: role of tenascins in tissue formation, cell adhesion modulation, regulation of proliferation and
    [Show full text]
  • Data Supplement
    Cell-specific ablation of Hsp47 defines the collagen producing cells in the injured heart Hadi Khalil,1 Onur Kanisicak,1,2 Ronald J. Vagnozzi,1Anne Katrine Johansen,1 Bryan D. Maliken,1 Vikram Prasad,1 Justin G. Boyer,1 Matthew J. Brody,1 Tobias Schips,1 Katja K. Kilian,1 Robert N. Correll,1,3 Kunito Kawasaki,4 Kazuhiro Nagata,4 Jeffery D. Molkentin1,5 1Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA 2Department of Pathology, University of Cincinnati, Cincinnati, Ohio, USA 3Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA 4Institute for Protein Dynamics, Kyoto Sangyo University, Kyoto, Japan 5Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Data Supplement -Supplemental Figures 1-7 -Supplemental Tables 1-3 Culture A Adβgal AdCre 100 µm CHP eGFP R26eGFP; Postn-MCM B 0.05 Hearts # R26eGFP; Hsp47fl/fl-Postn-MCM 0.04 * Supplemental Figure 1. Deletion of Hsp47 leads to collagen 0.03 aggregates in cultured fibroblasts and cell death in vivo. (A) Adult primary heart fibroblasts were isolated from R26eGFP Hsp47-loxP 0.02 TUNEL (%) TUNEL * targeted mice and infected with Adβgal or AdCre. Seventy-two hours later cells were processed for collagen-hybridizing peptide 0.01 immunofluorescence (red), showing collagen aggregates when Hsp47 was deleted, which was not observed in Adβgal controls. Fibroblast 0 Sham identity was shown by eGFP staining in the AdCre infected conditions. TAC Three separate experiments gave similar results. (B) TUNEL staining showing cell death levels in hearts of the indicated mice after 4 weeks post TAC.
    [Show full text]