Periostin attenuates tumor growth by inducing apoptosis in colitis-related colorectal cancer.

Yusuke Shimoyama,Kennichi Satoh,Keiichi Tamai,Yoichi Kakuta,Mao Nakamura,Ikuro Sato,Yoshitaka Kinouchi,Mai Mochizuki,Tooru Shimosegawa,Rie Shibuya,Kazunori Yamaguchi,Akira Kudo

doi:10.18632/oncotarget.25026

Abstract

Inflammatory bowel diseases, which are multifactorial autoimmune colitis diseases, are occurring with increasing prevalence. One of the most serious complications of these diseases is colorectal cancer. Here we investigated the role of periostin (Postn), a matricellular protein that interacts with various integrin molecules on the cell surface, in colitis-induced colorectal cancer. Immunohistochemistry of mouse and human colorectal cancer samples revealed that Postn was expressed in the stroma and was upregulated in close proximity to the cancer cells. The colonic tumorigenesis in an inflammation-related colon carcinogenesis mouse model was increased in Postn knock-out (Postn−/−) mice compared to Postn+/+ mice. Although no difference was found in the degree of colitis between Postn+/+ and Postn−/− mice, Postn inhibited tumor growth and induced the apoptosis of mouse rectal cancer cells in vitro. Furthermore, fewer apoptotic colorectal cancer cells were observed in Postn−/− than in Postn+/+ mice. These data suggested that Postn has an anti-tumor effect on colitis-induced colorectal cancer.

Highlights

Ulcerative colitis (UC) is a common type of inflammatory bowel disease (IBD)
Based on a literature search of the 20 genes that were most differentially expressed as identified by the weighted average difference (WAD) algorithm (Figure 4C), we focused on Bnip3 (Bcl2interaciting protein 3), because it was previously identified as a key factor in apoptosis
transforming growth factor-β (TGF-ß) promotes the secretion of Postn [17], and TGF-ß secreted by epithelial cancer cells exerts a paracrine influence on stromal cells, resulting in an increased production of extracellular matrix [18]

Summary

Introduction

Ulcerative colitis (UC) is a common type of inflammatory bowel disease (IBD). IBD is associated with chronic inflammation of the digestive tract, resulting in abdominal pain, persistent diarrhea, and hematochezia. Anti-tumor necrosis factor (TNF) agents are effective for attaining and maintaining IBD remission. Colorectal cancer (CRC) is one of the leading non-smoking-related cancers. This malignancy is one of the most serious complications of IBD, including UC [2], and the risk of CRC increases with the severity and duration of the IBD. Surgical resection is the primary treatment for CRC. Research has focused on finding novel agents targeting the CRC tumor’s angiogenic activity and cell growth (i.e., VEGF and EGF), these patients often die from recurrence and dissemination of the cancer soon after surgery. New strategies for improving the prognosis and individualized treatment of this cancer are urgently needed

Methods

Results

Conclusion