Review
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2014; 20(47): 17804-17818
Published online Dec 21, 2014. doi: 10.3748/wjg.v20.i47.17804
Cancer-associated fibroblasts in digestive tumors
Lei Huang, A-Man Xu, Sha Liu, Wei Liu, Tuan-Jie Li
Lei Huang, A-Man Xu, Tuan-Jie Li, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Lei Huang, Wei Liu, Tuan-Jie Li, Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Sha Liu, Department of Medical Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Wei Liu, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Author contributions: Huang L, Xu AM, Liu S and Liu W designed the research; Huang L and Li TJ performed the research; Huang L wrote the paper; Xu AM, Liu S, Liu W and Li TJ critically reviewed the paper; Huang L, Xu AM and Liu S critically revised the paper.
Correspondence to: Lei Huang, MD, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui Province, China. huangleizhenting@126.com
Telephone: +86-551-65334247 Fax: +86-551-63633742
Received: April 5, 2014
Revised: June 22, 2014
Accepted: July 11, 2014
Published online: December 21, 2014
Abstract

The significant influence of tumor stroma on malignant cells has been extensively investigated in this era of targeted therapy. The tumor microenvironment, as a dynamic system, is orchestrated by various cells including tumor vascular composing cells, inflammatory cells and fibroblasts. As a major and important component in tumor stroma, increasing evidence has shown that spindle-shaped cancer-associated fibroblasts (CAFs) are a significant modifier of cancer evolution, and promote tumorigenesis, tumor invasion and metastasis by stimulating angiogenesis, malignant cell survival, epithelial-mesenchymal transition (EMT) and proliferation via direct cell-to-cell contact or secretion of soluble factors in most digestive solid tumors. CAFs are thought to be activated, characterized by the expression of α-smooth muscle actin, fibroblast activated protein, fibroblast specific protein, vimentin, fibronectin, etc. They are hypothesized to originate from normal or aged fibroblasts, bone marrow-derived mesenchymal cells, or vascular endothelial cells. EMT may also be an important process generating CAFs, and most probably, CAFs may originate from multiple cells. A close link exists between EMT, tumor stem cells, and chemo-resistance of tumor cells, which is largely orchestrated by CAFs. CAFs significantly induce immunosuppression, and may be a prognostic marker in various malignancies. Targeted therapy toward CAFs has displayed promising anticancer efficacy, which further reinforces the necessity to explore the relationship between CAFs and their hosts.

Keywords: Cancer-associated fibroblast, Tumor progression, Epithelial-mesenchymal transition, Tumor immunity, Targeted therapy

Core tip: As a dominant component in tumor stroma, cancer-associated fibroblasts (CAFs) promote tumorigenesis, and tumor progression by stimulating angiogenesis, malignant cell survival, epithelial-mesenchymal transition (EMT) and proliferation via direct cell-to-cell contact or secretion of soluble factors in most digestive solid tumors. CAFs are characterized by the expression of α-smooth muscle actin, fibroblast activated protein, fibroblast specific protein, vimentin, etc. They are hypothesized to originate from various cells. EMT may also be an important process generating CAFs. A close link exists between CAFs-induced EMT, chemo-resistance of tumor cells, and tumor stem cells. CAFs significantly induce immunosuppression, and may be a prognostic marker. Targeted therapy toward CAFs has displayed promising anticancer efficacy.