Oncotarget

Research Papers:

CD147 and downstream ADAMTSs promote the tumorigenicity of Kaposi’s sarcoma-associated herpesvirus infected endothelial cells

Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole and Zhiqiang Qin _

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Oncotarget. 2016; 7:3806-3818. https://doi.org/10.18632/oncotarget.6584

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Abstract

Lu Dai1,3, Jimena Trillo-Tinoco4, Yihan Chen1, Karlie Bonstaff3, Luis Del Valle4, Chris Parsons3, Augusto C. Ochoa5, Jovanny Zabaleta5, Bryan P. Toole6, Zhiqiang Qin1,2

1Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

2Departments of Microbiology/Immunology/Parasitology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA

3Department of Medicine, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA

4Department of Pathology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA

5Department of Pediatrics, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA

6Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina and Hollings Cancer Center, Charleston, SC 29425, USA

Correspondence to:

Zhiqiang Qin, e-mail: zqin@lsuhsc.edu

Keywords: KSHV, Kaposi’s sarcoma, CD147, microarray

Received: August 26, 2015     Accepted: November 25, 2015     Published: December 12, 2015

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.


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