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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2015 > Volume 11 Number 4 > Xiao-Jun Shen1, Hao Zhang2*, Gu-Sheng Tang3, Xu-Dong Wang1, Rui Zheng1, Yang Wang4, Yan Zhu4, Xu-Chao Xue1, Jian-Wei Bi1

Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer

Xiao-Jun Shen1, Hao Zhang2*, Gu-Sheng Tang3, Xu-Dong Wang1, Rui Zheng1, Yang Wang4, Yan Zhu4, Xu-Chao Xue1, Jian-Wei Bi1
1. Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China; 2. Department of General Surgery, No. 411 Hospital of Navy, People’s Liberation Army, Shanghai, China 3. Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China; 4. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China These authors contributed equally to this work.  Corresponding author: Gu-sheng Tang, M.D., Ph.D. Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China; E-mail: drake015@163.com; Jian-wei Bi, M.D., Ph.D. Department of General Surgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, China, 200433; E-mail: bijianwei82@163.com; Fax: (86)-021-31161585.
Abstract :

Stromal fibroblasts play an important role in chronic cancer-related inflammation and the development as well as progression of malignant diseases. However, the difference and relationship between inflammation-associated fibroblasts (IAFs) and cancer-associated fibroblasts (CAFs) are poorly understood. In this study, gastric cancer-associated fibroblasts (GCAFs) and their corresponding inflammation-associated fibroblasts (GIAFs) were isolated from gastric cancer (GC) with chronic gastritis and cultured in vitro. These activated fibroblasts exhibited distinct secretion and tumor-promoting behaviors in vitro. Using proteomics and bioinformatics techniques, caveolin-1 (Cav-1) was identified as a major network-centric protein of a sub-network consisting of 121 differentially expressed proteins between GIAFs and GCAFs. Furthermore, immunohistochemistry in a GC cohort showed significant difference in Cav-1 expression score between GIAFs and GCAFs and among patients with different grades of chronic gastritis. Moreover, silencing of Cav-1 in GIAFs and GCAFs using small interfering RNA increased the production of pro-inflammatory and tumor-enhancing cytokines and chemokines in conditioned mediums that elevated cell proliferation and migration when added to GC cell lines AGS and MKN45 in vitro. In addition, Cav-1 status in GIAFs and GCAFs independently predicted the prognosis of GC. Our findings indicate that Cav-1 loss contributes to the distinct activation statuses of fibroblasts in GC microenvironment and gastritis mucosa, and Cav-1 expression in both GCAFs and GIAFs may serve as a potential biomarker for GC progression.

Keywords :
Cav-1, biomarker, gastric cancer

Date Deposited : 22 Feb 2016 09:58

Last Modified : 22 Feb 2016 09:58

Official URL: http://www.ijbs.com/v11i4

Volume 11, Number 4, - 2015 , ISSN 1449-2288

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