title: CD147 and downstream ADAMTSs promote the tumorigenicity of Kaposi's sarcoma-associated herpesvirus infected endothelial cells.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up-regulation of IL-6 and VEGF. By using a KS-like nude mouse model, we found that targeting CD147 and downstream ADAMTSs significantly suppressed KSHV-induced tumorigenesis in vivo. Taken together, targeting CD147 and associated proteins may represent a promising therapeutic strategy against these KSHV-related malignancies.
authors.affiliation: Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.|Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Jimena
authors.initials: J
authors.lastname: Trillo-Tinoco
authors.affiliation: Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Karlie
authors.initials: K
authors.lastname: Bonstaff
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.affiliation: Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Parsons
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Augusto C
authors.initials: AC
authors.lastname: Ochoa
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Jovanny
authors.initials: J
authors.lastname: Zabaleta
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina and Hollings Cancer Center, Charleston, SC 29425, USA.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.affiliation: Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.|Departments of Microbiology/Immunology/Parasitology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Qin
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000818:Animals; D017209:Apoptosis; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D020869:Gene Expression Profiling; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D023041:Xenograft Model Antitumor Assays
chemical_list: C497886:BSG protein, human; D012333:RNA, Messenger; D051926:Basigin; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human
keywords: CD147; KSHV; Kaposi’s sarcoma; microarray