Int J Biol Sci 2015; 11(4):370-379. doi:10.7150/ijbs.10666 This issue Cite

Research Paper

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.

Citation:
Shen XJ, Zhang H, Tang GS, Wang XD, Zheng R, Wang Y, Zhu Y, Xue XC, Bi JW. Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer. Int J Biol Sci 2015; 11(4):370-379. doi:10.7150/ijbs.10666. https://www.ijbs.com/v11p0370.htm
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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


Citation styles

APA
Shen, X.J., Zhang, H., Tang, G.S., Wang, X.D., Zheng, R., Wang, Y., Zhu, Y., Xue, X.C., Bi, J.W. (2015). Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer. International Journal of Biological Sciences, 11(4), 370-379. https://doi.org/10.7150/ijbs.10666.

ACS
Shen, X.J.; Zhang, H.; Tang, G.S.; Wang, X.D.; Zheng, R.; Wang, Y.; Zhu, Y.; Xue, X.C.; Bi, J.W. Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer. Int. J. Biol. Sci. 2015, 11 (4), 370-379. DOI: 10.7150/ijbs.10666.

NLM
Shen XJ, Zhang H, Tang GS, Wang XD, Zheng R, Wang Y, Zhu Y, Xue XC, Bi JW. Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer. Int J Biol Sci 2015; 11(4):370-379. doi:10.7150/ijbs.10666. https://www.ijbs.com/v11p0370.htm

CSE
Shen XJ, Zhang H, Tang GS, Wang XD, Zheng R, Wang Y, Zhu Y, Xue XC, Bi JW. 2015. Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer. Int J Biol Sci. 11(4):370-379.

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