DOCSLIB.ORG

Clinical Significance of Transmembrane 4 Superfamily in Colon Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Significance of Transmembrane 4 Superfamily in Colon Cancer British Journal of Cancer (2003) 89, 158 – 167 & 2003 Cancer Research UK All rights reserved 0007 – 0920/03 $25.00 www.bjcancer.com Clinical significance of transmembrane 4 superfamily in colon cancer 1,5 2 1 1 1 3 5 4 H Hashida , A Takabayashi , T Tokuhara , N Hattori , T Taki , H Hasegawa , S Satoh , N Kobayashi , 5 ,1 Y Yamaoka and M Miyake* 1 Department V of Oncology and Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20, Ohgimachi, 2 Kita-ku, Osaka 530-8480, Japan; Department of Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20, Ohgimachi, Kita-ku, Osaka, 530-8480, Japan; 3First Department of Internal Medicine, Ehime University School of Medicine, Oazashizukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan; 4First Department of Surgery, Ehime University School of Medicine, Oazashizukawa, Shigenobu-cho, Onsen-gun, Ehime 791- 5 0295, Japan; Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan Cell motility is an important cellular function closely related to the processes of tumour progression and metastasis. Several members of transmembrane 4 superfamily (TM4SF) have been reported to be associated with cell motility and metastatic potential of solid tumour. The aim of this study is to clarify the clinical significance of the member of TM4SF (MRP-1/CD9, KAI1/CD82 and CD151) in Molecular and Cellular Pathology human colon cancer. We studied 146 colon cancer patients who underwent curative surgery and studied the expression of MRP-1/ CD9, KAI1/CD82 and CD151 using reverse transcriptase – polymerase chain reaction and immunohistochemistry. We found that 64 patients (43.8%) had MRP-1/CD9-positive tumours and that the overall survival rate of patients with MRP-1/CD9-positive tumours was much higher than that of patients with MRP-1/CD9-negative tumours (89.8 vs 50.8%, Po0.001). In contrast, 63 patients (43.2%) had KAI1/CD82-positive tumours and the overall survival rate of patients with KAI1/CD82-positive tumours was also higher than that of patients with KAI1/CD82-negative tumours (84.8 vs 54.9%, P ¼ 0.002). On the other hand, positive CD151 expression had a bad effect on the overall survival rate of patients with colon cancer (61.2 vs 74.9%, P ¼ 0.022). In a multivariate analysis, MRP-1/CD9 status was a good indicator of the overall survival (P ¼ 0.007). We have shown that the reduction of MRP-1/CD9 and KAI1/CD82 expression, and the increasing CD151 expression are indicators for a poor prognosis in patients with colon cancer. This is a first report describing about the relation between CD151 and colon cancer. British Journal of Cancer (2003) 89, 158–167. doi:10.1038/sj.bjc.6601015 www.bjcancer.com & 2003 Cancer Research UK Keywords: TM4SF; MRP-1/CD9; KAI1/CD82; CD151; colon cancer Cell motility plays an important key function related to the process of unequal size, as well as a particular fold in the large extracellular of tumour progression and metastasis (Miyake and Hakomori, loop (Wright and Tomlinson, 1994). 1991). It is partially dependent on adhesion molecules and KAI1/CD82 is also a member of TM4SF. KAI1/CD82 expression proteases (Hashida et al, 2001, 2002a). Previously, we reported suppressed experimental metastasis of rat prostate tumour cells that the motility-related protein-1 (MRP-1) is an antigen (Dong et al, 1995), and decreased motility and invasion of colon recognised by monoclonal antibody (MAb) M31-15 which inhibits carcinoma cells (Takaoka et al, 1998). KAI1/CD82 is considered to cell motility and the MRP-1 sequence coincides with the cluster of be a metastasis-suppressor gene of prostate cancer and low KAI1/ differentiation antigen 9 (CD9) (Miyake et al, 1991). In our CD82 expression has been reported to be involved in the malignant previous reports, we showed MRP-1/CD9-overexpressing tumour progression of prostate cancer (Dong et al, 1996). We also showed cells negative cell motility and metastatic potential (Ikeyama et al, that decreased KAI1/CD82 gene expression was an indicator of 1993). Therefore, MRP-1/CD9 regulates cell motility and is a poor prognosis in lung cancer (Adachi et al, 1996), breast cancer receptor for negative signal ligands. In addition, negative MRP-1/ (Huang et al, 1998) and pancreatic cancer (Sho et al, 1998). These CD9 expression was associated with a poor prognosis in breast data show that KAI1/CD82 is an important tumour suppressor cancer (Miyake et al, 1996), lung cancer (Higashiyama et al, 1995) gene in cancer metastasis and progression. and pancreatic cancer (Sho et al, 1998). These data also suggest On the other hand, CD151 is also a transmembrane molecule that MRP-1/CD9 expression might be associated with metastatic that has been characterised as a member of the evolutionally ability and degree of malignancy. MRP-1/CD9 belongs to the conserved TM4SF, and it is known as SFA-1 and PETA-3 (Fitter transmembrane 4 superfamily (TM4SF), which is characterised by et al, 1995; Hasegawa et al, 1996). CD151 cDNA shows an open four transmembrane domains delimiting two extracellular regions reading frame of 253 amino acids that encodes a protein of molecular mass 28 kDa. In addition, human CD151 gene locates on *Correspondence: Dr M Miyake; E-mail: [email protected]. chromosome 11p15.1. CD151 in involved in cell adhesion, cell Received 18 October 2002; revised 12 March 2003; accepted 23 March motility, metastasis, and stability and formation of hemidesmo- 2003 somes (Yauch et al, 1998). TM4SF in colon cancer H Hashida et al 159 Several members of TM4SF are associated with the metastatic patients were men and 62 were women. The median age of the phenotype. In addition, for the most part, they work negatively. patients was 62.8 years, with a range of 35–80 years. The patients Recently, it was reported to be the first member of the TM4SF to could be broken down into 25 with pathological stage I, 46 with show signs of being a positive effecter of metastasis (Testa et al, stage II and 75 with stage III disease. The mean follow-up period 1999). Moreover, CD151 enhances cell motility and cancer for all patients was 44.3 months, with a range of 6.3–85.9 months. metastasis (Kohno et al, 2002) and CD151 overexpression leads to a poor prognosis of the patients with non-small cell lung cancer (Tokuhara et al, 2001). Therefore, CD151 is a metastasis-associated Tumour specimens antigen that appears to contribute to the metastatic phenotype One-half of each fresh tumour tissue specimen was immediately positively. These findings set CD151 apart from MRP-1/CD9 and embedded in optimum cutting temperature compound (Miles, KAI1/CD82 that appear to act as metastasis-suppressor genes. It Kankakee, IL, USA), and frozen in liquid nitrogen immediately may contribute to the collapse of tetraspanin/tetraspanin com- after surgical resection and maintained at À801C until use. Frozen plexes. In addition, no consistent findings have been reported as a sections were cut on a cryostat to a thickness of 6 mm and were prognostic indicator for CD151 gene in colon cancer. As part of stained with haematoxylin and eosin and used for immunohisto- our evaluation of members of the TM4SF as possible prognostic chemical staining. After the connective tissues were trimmed off, predictors, we performed a retrospective study on the expression the other-half of the tumour specimen that was then made up of of the MRP-1/CD9 gene, the recently identified KAI1/CD82 gene more than 80% cancer cells was used for the reverse transcriptase– and the CD151 gene in human colon cancer. polymerase chain reaction (RT–PCR) analysis. MATERIALS AND METHODS Immunohistochemical assays Clinical characteristics of the patients The assays were carried out as described previously (Hashida et al, 2002a). Endogenous peroxidases were blocked by incubating with We studied 146 patients with up to stage III colon cancer who had 0.3% H2O2 in absolute methanol for 30 min. The sections were then undergone surgery at the Department of Surgery of the Kitano incubated with 5% bovine serum albumin for 2 h at room Hospital between October 1994 and May 2001. All patients temperature. Subsequently, replicate sections were incubated for underwent curative surgery. The postsurgical staging of each 2 h with the anti-MRP-1/CD9 MAb M31-15, the anti-KAI1/CD82 tumour was classified according to the tumour–node–metastasis MAb C33 and the anti-CD151 MAb SFA1.2B4, respectively. After (TNM) staging system (Sobin and Wittekind, 1997). The clinical washing three times in phosphate-buffered saline (PBS), they were characteristics of the patients are presented in Table 1. In all, 84 of then incubated for 1 h with biotinylated horse anti-mouse IgG Table 1 Relation of MRP-1/CD9, KAI1/CD82 and CD151 expression and various prognostic factors in 146 patients with colon cancer MRP-1/CD9 KAII/CD82 CD151 Clinicopathological Number of characteristics patients Positive Negative P-value Positive Negative P-value Positive Negative P-value Age (years) p60 74 35 39 NS 33 41 NS 35 39 NS X60 72 29 43 30 42 46 26 Sex Female 62 29 33 NS 29 33 NS 32 30 NS Male 84 35 49 34 50 49 35 Molecular and Cellular Pathology Tumour status T1 17 9 8 NS 11 6 NS 9 8 0.025 T2 20 8 12 7 13 12 8 T3 83 38 45 38 45 39 44 T4 26 9 17 7 19 21 5 Nodal status N0 71 39 32 0.007 43 28 o0.001 37 34 NS N1 33 14 19 11 22 15 18 N2 42 11 31 9 33 29 13 Pathological stage I 25 13 12 0.030 15 10 o0.001 15 10 NS II 46 26 20 28 18 22 24 III 75 25 50 20 55 44 31 Differentiation Well 32 16 16 NS 18 14 NS 14 18 NS Moderately 101 42 59 40 61 57 44 Poorly 13 6 7 5 8 10 3 Total 146 64 82 63 83 81 65 NS ¼ not significant.
Load more

Recommended publications
  • Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis.
    [Show full text]
  • RI-Mediated Mast Cell Activation Ε of Fc Tetraspanin CD151 Is A
    Tetraspanin CD151 Is a Negative Regulator of Fc εRI-Mediated Mast Cell Activation Hiam Abdala-Valencia, Paul J. Bryce, Robert P. Schleimer, Joshua B. Wechsler, Lucas F. Loffredo, Joan M. Cook-Mills, This information is current as Chia-Lin Hsu and Sergejs Berdnikovs of September 26, 2021. J Immunol 2015; 195:1377-1387; Prepublished online 1 July 2015; doi: 10.4049/jimmunol.1302874 http://www.jimmunol.org/content/195/4/1377 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2015/07/01/jimmunol.130287 Material 4.DCSupplemental http://www.jimmunol.org/ References This article cites 63 articles, 28 of which you can access for free at: http://www.jimmunol.org/content/195/4/1377.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 26, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Tetraspanin CD151 Is a Negative Regulator of Fc«RI-Mediated Mast Cell Activation Hiam Abdala-Valencia,* Paul J.
    [Show full text]
  • Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
    Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only.
    [Show full text]
  • Derivation of Induced Pluripotent Stem Cells from Pig Somatic Cells
    Derivation of induced pluripotent stem cells from pig somatic cells Toshihiko Ezashia, Bhanu Prakash V. L. Telugua, Andrei P. Alexenkoa, Shrikesh Sachdevb, Sunilima Sinhaa, and R. Michael Robertsa,b,1 Divisions of aAnimal Sciences and bBiochemistry, University of Missouri, Columbia, MO 65211 Contributed by R. Michael Roberts, May 13, 2009 (sent for review April 15, 2009) For reasons that are unclear the production of embryonic stem cells For reasons that are unclear, the establishment of porcine ESC from ungulates has proved elusive. Here, we describe induced from ICM of blastocysts and the epiblast of slightly older pluripotent stem cells (iPSC) derived from porcine fetal fibroblasts embryos has proven to be elusive. There has been a similar lack by lentiviral transduction of 4 human (h) genes, hOCT4,hSOX2, of success with other ungulate species. The earliest reports hKLF4, and hc-MYC, the combination commonly used to create iPSC announcing the derivation of ESC-like cells from ICM of pigs in mouse and human. Cells were cultured on irradiated mouse appeared in the early 1990s (19–21), but these ESC-like cells and embryonic fibroblasts (MEF) and in medium supplemented with many others since then, including ones for cattle, goat, and knockout serum replacement and FGF2. Compact colonies of alka- sheep, as well as for pig, have failed to meet the full criteria to line phosphatase-positive cells emerged after Ϸ22 days, providing define them as ESC (11–13). There are a number of reasons that an overall reprogramming efficiency of Ϸ0.1%. The cells expressed might explain the problems encountered, including choice of the porcine OCT4, NANOG, and SOX2 and had high telomerase activity, wrong stage of embryo development to establish the cultures, inappropriate culture and cell passage conditions, and contam- but also continued to express the 4 human transgenes.
    [Show full text]
  • Dynamics Within Tetraspanin Pairs Affect MHC Class II Expression
    328 Research Article Dynamics within tetraspanin pairs affect MHC class II expression Tineke van den Hoorn, Petra Paul, Lennert Janssen, Hans Janssen and Jacques Neefjes* Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands *Author for correspondence ([email protected]) Accepted 11 August 2011 Journal of Cell Science 125, 328–339 ß 2012. Published by The Company of Biologists Ltd doi: 10.1242/jcs.088047 Summary Late endosomal multivesicular bodies (MVBs) are complicated organelles with various subdomains located at the limiting membrane and the internal vesicles (ILVs). ILVs accumulate tetraspanins such as CD63 and CD82 that might form protein assemblies, including major histocompatibility complex class II (MHC-II) and its chaperone human leukocyte antigen (HLA)-DM. Here, we studied the effect of four late endosomal tetraspanin proteins on MHC-II expression. Silencing CD9, CD63 and CD81 enhanced MHC-II expression whereas silencing CD82 did not. No effect on peptide loading was observed. Using confocal FRET technology, we measured the dynamics of CD63 and CD82 interaction with MHC-II and its chaperone HLA-DM. CD63–CD82 interactions remained unaltered in the two MVB subdomains whereas the interactions between CD63 or CD82 homologous pairs changed. CD63 stably associated with MHC- II, and CD82 with HLA-DM, on both MVB subdomains whereas the CD82–MHC-II and CD63–HLA-DM interactions changed. These data visualize for the first time the protein dynamics of tetraspanin assemblies in MVB
    [Show full text]
  • A Shared Pathway of Exosome Biogenesis Operates at Plasma And
    bioRxiv preprint doi: https://doi.org/10.1101/545228; this version posted February 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. A shared pathway of exosome biogenesis operates at plasma and endosome membranes Francis K. Fordjour1, George G. Daaboul2, and Stephen J. Gould1* 1Department of Biological Chemistry Johns Hopkins University Baltimore, MD USA 2Nanoview Biosciences Boston, MA USA Corresponding author: Stephen J. Gould, Ph.D. Department of Biological Chemistry Johns Hopkins University Baltimore, MD USA Email: [email protected] Tel (01) 443 847 9918 1 bioRxiv preprint doi: https://doi.org/10.1101/545228; this version posted February 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Summary: This study of exosome cargo protein budding reveals that cells use a common pathway for budding exosomes from plasma and endosome membranes, providing a new mechanistic explanation for exosome heterogeneity and a rational roadmap for exosome engineering. Keywords: Protein budding, tetraspanin, endosome, plasma membrane, extracellular vesicle, CD9, CD63, CD81, SPIR, interferometry Abbreviations: EV, extracellular vesicles; IB, immunoblot; IFM, immunofluorescence microscopy; IPMC, intracellular plasma membrane-connected compartment; MVB, multivesicular body; SPIR, single-particle interferometric reflectance; SPIRI, single-particle interferometric reflectance imaging 2 bioRxiv preprint doi: https://doi.org/10.1101/545228; this version posted February 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved.
    [Show full text]
  • Expression of the Tetraspanins CD9, CD37, CD63, and CD151 in Merkel Cell Carcinoma: Strong Evidence for a Posttranscriptional Fine-Tuning of CD9 Gene Expression
    Modern Pathology (2010) 23, 751–762 & 2010 USCAP, Inc. All rights reserved 0893-3952/10 $32.00 751 Expression of the tetraspanins CD9, CD37, CD63, and CD151 in Merkel cell carcinoma: strong evidence for a posttranscriptional fine-tuning of CD9 gene expression Markus Woegerbauer1, Dietmar Thurnher1, Roland Houben2, Johannes Pammer3, Philipp Kloimstein1, Gregor Heiduschka1, Peter Petzelbauer4 and Boban M Erovic1 1Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria; 2Department of Dermatology, Medical University of Wuerzburg, Germany; 3Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria and 4Department of Dermatology, Medical University of Vienna, Vienna, Austria Tetraspanins including CD9, CD37, CD63, and CD151 are linked to cellular adhesion, cell differentiation, migration, carcinogenesis, and tumor progression. The aim of the study was to detect, quantify, and evaluate the prognostic value of these tetraspanins in Merkel cell carcinoma and to study the regulation of CD9 mRNA expression in Merkel cell carcinoma cell lines in detail. Immunohistochemical staining of 28 Merkel cell carcinoma specimens from 25 patients showed a significant correlation of CD9 (P ¼ 0.03) and CD151 (P ¼ 0.043) expression to overall survival. CD9 and CD63 expression correlated significantly to patients’ disease-free interval (P ¼ 0.017 and P ¼ 0.058). Of primary Merkel cell carcinoma tumors, 42% were CD9 positive in contrast to only 21% of the subcutaneous in-transit metastases. Characterization of the 50 untranslated region (UTR) of the CD9 mRNA from two cultured Merkel cell carcinoma cell lines revealed the presence of two major RNA species differing only in the length of their 50 termini (183 versus 102 nucleotides).
    [Show full text]
  • Kruppel-Like Factor 9 Inhibits Glioblastoma Stemness
    KRUPPEL-LIKE FACTOR 9 INHIBITS GLIOBLASTOMA STEMNESS THROUGH GLOBAL TRANSCRIPTION REPRESSION AND INHIBITION OF INTEGRIN ALPHA 6 AND CD151 By Jessica Tilghman A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland October, 2015 Abstract Glioblastoma (GBM) stem cells (GSCs) represent tumor-propagating cells with stem-like characteristics (stemness) that contribute disproportionately to GBM drug resistance and tumor recurrence. Understanding the mechanisms supporting GSC stemness is important for developing novel strategies that target tumor propagation to inhibit cancer progression and improve patient survival. Krüppel-like factor 9 (KLF9) has emerged as a regulator of cell differentiation, neural development, and oncogenesis; however, the molecular basis for KLF9’s diverse contextual functions has been unclear. We establish for the first time a genome-wide map of KLF9-regulated targets in human glioblastoma stem-like cells, and show that KLF9 functions as a transcriptional repressor and thereby regulates multiple signaling pathways involved in oncogenesis and regulation of cancer stem-like phenotype. A detailed analysis of two novel KLF9 targets suggests that KLF9 inhibits glioma cell stemness by repressing expression of integrin α6 and CD151. The expression of one candidate KLF9 target gene ITGA6 coding for integrin α6 was verified to be downregulated by KLF9 in GSCs. ITGA6 transcription repression by KLF9 altered GBM neurosphere cell behavior as evidenced by reduced cell adhesion to and migration through membrane coated with the integrin α6 ligand laminin. Forced expression of integrin α6 partially rescued GBM neurosphere cells from the differentiating and adhesion/migration-inhibiting effects of KLF9.
    [Show full text]
  • Human Eosinophils and Their Activation by Allergens Via Danger
    Human eosinophils and their activation by allergens via danger signal receptors Elin Redvall ______________________ 2010 Department of Infectious diseases, Institute of Biomedicine, The Sahlgrenska Academy Cover illustration photo: Kerstin Andersson (Eosinophils) Abstract Human eosinophilic granulocytes are polymorphonuclear cells with a powerful arsenal of cytotoxic substances in their granules, which are mainly found in the gastrointestinal mucosa, and the respiratory and genitourinary tracts. Their physiological role is incompletely understood, although it is likely they protect the mucosal surfaces, perhaps by recognizing danger signals present on microorganisms or released from damaged tissue. We have earlier shown that eosinophils can recognize and become directly activated by aeroallergens such as house dust mite (HDM) and birch pollen. Eosinophils exposed to (HDM) release both of the cytotoxic granule proteins eosinophil peroxidase (EPO) and major basic protein, whereas birch pollen extract only triggers EPO release. Here we further investigate which receptors on eosinophils are used to signal the presence of HDM and birch pollen. Recognition was found to be mediated by the formyl peptide receptors (FPRs) FPR1 and FPR2. We also characterized the expression of this family of receptors in human eosinophils and found that they express FPR1 and FPR2, but not FPR3, similar to neutrophilic granulocytes. We also discovered that signaling through FPR1 can desensitize the eotaxin-1 receptor CCR3 rendering the cells anergic with respect to chemotaxis in response to eotaxin-1, but not regarding respiratory burst. Hence, there is cross- talk between these two receptors regarding one important effector function of eosinophils. Eosinophilic reactivity in vitro to the aeroallergens HDM, birch pollen, timothy grass pollen and cat dander did not differ between individuals with allergy and healthy individuals.
    [Show full text]
  • Tetraspanin CD151 Plays a Key Role in Skin Squamous Cell Carcinoma
    Oncogene (2013) 32, 1772–1783 & 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13 www.nature.com/onc ORIGINAL ARTICLE Tetraspanin CD151 plays a key role in skin squamous cell carcinoma QLi1, XH Yang2,FXu1, C Sharma1, H-X Wang1, K Knoblich1, I Rabinovitz3, SR Granter4 and ME Hemler1 Here we provide the first evidence that tetraspanin CD151 can support de novo carcinogenesis. During two-stage mouse skin chemical carcinogenesis, CD151 reduces tumor lag time and increases incidence, multiplicity, size and progression to malignant squamous cell carcinoma (SCC), while supporting both cell survival during tumor initiation and cell proliferation during the promotion phase. In human skin SCC, CD151 expression is selectively elevated compared with other skin cancer types. CD151 support of keratinocyte survival and proliferation may depend on activation of transcription factor STAT3 (signal transducers and activators of transcription), a regulator of cell proliferation and apoptosis. CD151 also supports protein kinase C (PKC)a–a6b4 integrin association and PKC-dependent b4 S1424 phosphorylation, while regulating a6b4 distribution. CD151–PKCa effects on integrin b4 phosphorylation and subcellular localization are consistent with epithelial disruption to a less polarized, more invasive state. CD151 ablation, while minimally affecting normal cell and normal mouse functions, markedly sensitized mouse skin and epidermoid cells to chemicals/drugs including 7,12-dimethylbenz[a]anthracene (mutagen) and camptothecin (topoisomerase inhibitor), as well as to agents targeting epidermal growth factor receptor, PKC, Jak2/Tyk2 and STAT3. Hence, CD151 ‘co-targeting’ may be therapeutically beneficial. These findings not only support CD151 as a potential tumor target, but also should apply to other cancers utilizing CD151/laminin-binding integrin complexes.
    [Show full text]
  • Pancancer Progression Human Vjune2017
    Gene Symbol Accession Alias/Prev Symbol Official Full Name AAMP NM_001087.3 - angio-associated, migratory cell protein ABI3BP NM_015429.3 NESHBP|TARSH ABI family, member 3 (NESH) binding protein ACHE NM_000665.3 ACEE|ARACHE|N-ACHE|YT acetylcholinesterase ACTG2 NM_001615.3 ACT|ACTA3|ACTE|ACTL3|ACTSG actin, gamma 2, smooth muscle, enteric ACVR1 NM_001105.2 ACTRI|ACVR1A|ACVRLK2|ALK2|FOP|SKR1|TSRI activin A receptor, type I ACVR1C NM_145259.2 ACVRLK7|ALK7 activin A receptor, type IC ACVRL1 NM_000020.1 ACVRLK1|ALK-1|ALK1|HHT|HHT2|ORW2|SKR3|TSR-I activin A receptor type II-like 1 ADAM15 NM_207195.1 MDC15 ADAM metallopeptidase domain 15 ADAM17 NM_003183.4 ADAM18|CD156B|CSVP|NISBD|TACE ADAM metallopeptidase domain 17 ADAM28 NM_014265.4 ADAM 28|ADAM23|MDC-L|MDC-Lm|MDC-Ls|MDCL|eMDC II|eMDCII ADAM metallopeptidase domain 28 ADAM8 NM_001109.4 CD156|MS2 ADAM metallopeptidase domain 8 ADAM9 NM_001005845.1 CORD9|MCMP|MDC9|Mltng ADAM metallopeptidase domain 9 ADAMTS1 NM_006988.3 C3-C5|METH1 ADAM metallopeptidase with thrombospondin type 1 motif, 1 ADAMTS12 NM_030955.2 PRO4389 ADAM metallopeptidase with thrombospondin type 1 motif, 12 ADAMTS8 NM_007037.4 ADAM-TS8|METH2 ADAM metallopeptidase with thrombospondin type 1 motif, 8 ADAP1 NM_006869.2 CENTA1|GCS1L|p42IP4 ArfGAP with dual PH domains 1 ADD1 NM_001119.4 ADDA adducin 1 (alpha) ADM2 NM_001253845.1 AM2|dJ579N16.4 adrenomedullin 2 ADRA2B NM_000682.4 ADRA2L1|ADRA2RL1|ADRARL1|ALPHA2BAR|alpha-2BAR adrenoceptor alpha 2B AEBP1 NM_001129.3 ACLP AE binding protein 1 AGGF1 NM_018046.3 GPATC7|GPATCH7|HSU84971|HUS84971|VG5Q
    [Show full text]
  • Extracellular Vesicle Human CD9/CD63/CD81 Antibody Panel
    Extracellular Vesicle Human CD9/CD63/CD81 Antibody Panel Antibody panel for the detection of extracellular vesicles using CD9, CD63, and CD81 markers Catalog #100-0211 1 Kit Product Description The Extracellular Vesicle Human CD9/CD63/CD81 Antibody Panel is suitable for the detection of extracellular vesicles (EVs) derived from human cells. It comprises three primary antibodies that are immunoreactive toward human CD9, CD63, and CD81; these are proteins that are typically expressed on EVs and widely used as markers to analyze and isolate these cell-derived particles. CD9, CD63, and CD81 belong to the tetraspanin family of membrane proteins, which possess four transmembrane domains and interact with diverse proteins on the cell surface to form multimolecular networks termed tetraspanin-enriched microdomains. CD9, CD63, and CD81 proteins are expressed on the surface of many cells, including B cells, T cells, NK cells, monocytes, dendritic cells, thymocytes, endothelial cells, and fibroblasts, and are involved in modulating a variety of cellular processes including cell activation, adhesion, differentiation, and tumor invasion. The antibodies provided in this panel have been reported for use in analyzing primary cells, cell lines, and EVs by ELISA, flow cytometry, immunocytochemistry, immunoprecipitation, and Western blotting. They have been reported to cross-react with their cognate antigens in non-human primates, including baboons and rhesus and cynomolgus macaques. Product Information The following products comprise the Extracellular
    [Show full text]