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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2016; 22(23): 5301-5316
Published online Jun 21, 2016. doi: 10.3748/wjg.v22.i23.5301
Fibroblasts, an inconspicuous but essential player in colon cancer development and progression
Naofumi Mukaida, Soichiro Sasaki
Naofumi Mukaida, Soichiro Sasaki, Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
Author contributions: Mukaida N wrote the manuscript; and Sasaki S participated in writing the manuscript and preparing the figure.
Conflict-of-interest statement: We have no financial conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Naofumi Mukaida, MD, PhD, Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. mukaida@staff.kanazawa-u.ac.jp
Telephone: +81-76-2646735 Fax: +81-76-2344520
Received: March 16, 2016
Peer-review started: March 20, 2016
First decision: April 14, 2016
Revised: April 22, 2016
Accepted: May 21, 2016
Article in press: May 23, 2016
Published online: June 21, 2016
Abstract

Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts (CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs.

Keywords: Angiogenesis, Drug resistance, Extracellular matrix, Immune evasion, Transforming growth factor-β, Invasion, Metastasis

Core tip: Tumor microenvironments have a crucial role in cancer initiation and progression, and consist of various types of cells, such as endothelial cells, leukocytes, and fibroblasts. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts (CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs.