title: Caveolin-1 is a modulator of fibroblast activation and a potential biomarker for gastric cancer.
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.
authors: 1. Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China;
authors: Xiao-Jun
authors: XJ
authors: Shen
authors: 2. Department of General Surgery, No. 411 Hospital of Navy, People's Liberation Army, Shanghai, China.
authors: Hao
authors: H
authors: Zhang
authors: 3. Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China;
authors: Gu-Sheng
authors: GS
authors: Tang
authors: 1. Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China;
authors: Xu-Dong
authors: XD
authors: Wang
authors: 1. Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China;
authors: Rui
authors: R
authors: Zheng
authors: 4. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Yang
authors: Y
authors: Wang
authors: 4. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Yan
authors: Y
authors: Zhu
authors: 1. Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China;
authors: Xu-Chao
authors: XC
authors: Xue
authors: 1. Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China;
authors: Jian-Wei
authors: JW
authors: Bi
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019295:Computational Biology; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D051242:Caveolin 1; D017077:Culture Media, Conditioned; D034741:RNA, Small Interfering
keywords: Cav-1; biomarker; gastric cancer