WISP-1, a novel angiogenic regulator of the CCN family, promotes oral squamous cell carcinoma angiogenesis through VEGF-A expression
| Autor: | Ching-Wen Tsao, Po-Chun Chen, Ching-Chia Lin, Shih-Wei Wang, An-Chen Chang, Chih-Hsin Tang, Ming-Yu Lein, Jing-Yuan Chuang, Chiao-Wen Lin |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Oncology medicine.medical_specialty Pathology Angiogenesis Biology Transfection VEGF-A CCN Intercellular Signaling Proteins Neovascularization angiogenesis Mice Cell Line Tumor Proto-Oncogene Proteins Internal medicine medicine Animals Humans Mouth neoplasm Tumor microenvironment Hematology Neovascularization Pathologic WISP-1 Squamous Cell Carcinoma of Head and Neck oral squamous cell carcinoma CTGF Head and Neck Neoplasms Tumor progression CYR61 Carcinoma Squamous Cell Heterografts Mouth Neoplasms medicine.symptom Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Jing-Yuan Chuang 1, * , Po-Chun Chen 2, 3, * , Ching-Wen Tsao 1 , An-Chen Chang 2 , Ming-Yu Lein 2, 4 , Ching-Chia Lin 5 , Shih-Wei Wang 6 , Chiao-Wen Lin 7, 8 , Chih-Hsin Tang 2, 9, 10 1 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan 2 Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan 3 Department of Medical Research, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan 4 Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 5 Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan 6 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan 7 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 8 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 9 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan 10 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan * These authors have contributed equally to this study Correspondence to: Chih-Hsin Tang, e-mail: chtang@mail.cmu.edu.tw Chiao-Wen Lin, e-mail: cwlin@csmu.edu.tw Keywords: WISP-1, VEGF-A, oral squamous cell carcinoma, angiogenesis Received: September 23, 2014 Accepted: December 19, 2014 Published: January 30, 2015 ABSTRACT Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by poor prognosis and a low survival rate. VEGF-A is the most established angiogenic factor involved in the angiogenic-regulated tumor progression. WISP-1/CCN4 is an extracellular matrix-related protein that belongs to the Cyr61, CTGF, Nov (CCN) family and regulates many biological functions, such as angiogenesis. Previous studies indicated the role of WISP-1 in tumor progression. However, the angiogenic property of WISP-1 in the cancer microenvironment has never been discussed. Here, we provide novel insights regarding the role of WISP-1 in the angiogenesis through promoting VEGF-A expression. In this study, the correlation of WISP-1 and VEGF-A was confirmed by IHC staining of specimens from patients with OSCC. In vitro results indicated that WISP-1 induced VEGF-A expression via the integrin αvβ3/FAK/c-Src pathway, which transactivates the EGFR/ERK/HIF1-α signaling pathway in OSCC. This pathway in turn induces the recruitment of endothelial progenitor cells and triggers the neovascularization in the tumor microenvironment. Our in vivo data revealed that tumor-secreted WISP-1 promoted the angiogenesis through VRGF expression and increased angiogenesis-related tumor growth. Our study offers new information that highlights WISP-1 as a potential novel therapeutic target for OSCC. |
| Databáze: | OpenAIRE |
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