Caveolin-1 is a modulator of fibroblast activation and a potential biomarker for gastric cancer.
Caveolin-1 is a modulator of fibroblast activation and a potential biomarker for gastric cancer.
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Caveolin-1 是成纤维细胞激活的调节剂和胃癌的潜在生物标志物
DOI：
10.7150/ijbs.10666
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发表时间：
2015
影响因子：
9.2
通讯作者：
Bi JW
中科院分区：
文献类型：
--
作者：
Shen XJ;Zhang H;Tang GS;Wang XD;Zheng R;Wang Y;Zhu Y;Xue XC;Bi JW
间质成纤维细胞在慢性肿瘤相关炎症和恶性疾病的发生发展中起重要作用。然而，炎症相关成纤维细胞（IAFs）和癌症相关成纤维细胞（CAFs）之间的差异和关系知之甚少。本研究从慢性胃炎胃癌组织中分离胃癌相关成纤维细胞（GCAFs）及其相应的炎症相关成纤维细胞（GIAFs），并进行体外培养。这些活化的成纤维细胞在体外表现出明显的分泌和促肿瘤行为。利用蛋白质组学和生物信息学技术，将Caveolin-1（Cav-1）鉴定为GIAFs和GCAFs之间121个差异表达蛋白组成的网络中的主要网络中心蛋白。此外，免疫组化在GC队列中显示GIAFs和GCAFs之间以及不同级别慢性胃炎患者之间Cav-1表达评分存在显著差异。此外，使用小干扰RNA沉默GIAFs和GCAFs中的Cav-1增加了条件培养基中促炎性和肿瘤增强性细胞因子和趋化因子的产生，当加入体外GC细胞系AGS和MKN 45时，这些细胞因子和趋化因子提高了细胞增殖和迁移。此外，GIAFs和GCAFs中的Cav-1状态独立预测GC的预后。我们的研究结果表明，Cav-1的损失有助于不同的激活状态的成纤维细胞在GC微环境和胃炎粘膜，和Cav-1的表达在GCAFs和GIAFs可能作为一个潜在的生物标志物GC的进展。
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.
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影响因子：
3.7
作者：
Cerami E;Demir E;Schultz N;Taylor BS;Sander C
通讯作者：
Sander C
影响因子：
4.3
作者：
Martinez-Outschoorn, Ubaldo E.;Pavlides, Stephanos;Sotgia, Federica
通讯作者：
Sotgia, Federica
影响因子：
3.4
作者：
SIPPONEN, P;KOSUNEN, TU;SEPPALA, K
通讯作者：
SEPPALA, K
影响因子：
11.2
作者：
Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.
影响因子：
16.8
作者：
Buckley, CD;Pilling, D;Salmon, M
通讯作者：
Salmon, M