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. 2018 Apr 13;9(28):20008-20017.
doi: 10.18632/oncotarget.25026.

Periostin Attenuates Tumor Growth by Inducing Apoptosis in Colitis-Related Colorectal Cancer

Free PMC article

Periostin Attenuates Tumor Growth by Inducing Apoptosis in Colitis-Related Colorectal Cancer

Yusuke Shimoyama et al. Oncotarget. .
Free PMC article


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.

Keywords: apoptosis; colitis; colorectal cancer; periostin.

Conflict of interest statement

CONFLICTS OF INTEREST The authors have no competing ethical or financial interests to declare.


Figure 1
Figure 1. Periostin expression in colorectal cancer
Colitis-induced colorectal cancer in mice (A to C), colorectal cancer of ulcerative colitis patients (D to F), and an allograft of CMT93 cells in NOG mice were stained with hematoxylin and eosin (A, D, and G), and with anti-Postn (B, E, and H), and anti-Ki67 (C, F, and I) antibodies. WT, wild-type; UC, ulcerative colitis.
Figure 2
Figure 2. Colitis-induced colorectal cancer development was facilitated in Postn−/− mice
(A) Macroscopic images of the large intestine from Postn+/+ and Postn−/− AOM/DSS-model mice. Arrowheads indicate colorectal tumors. (B) Hematoxylin and eosin staining of the adenocarcinoma in Postn+/+ and Postn−/− mice. Bar, 100 μm. (C) Quantification of the tumor surface area. The surface area was measured using ImageJ software. *P < 0.05. (D) Number of colorectal tumors in Postn+/+ and Postn−/− mice. Postn, Periostin. *P < 0.01.
Figure 3
Figure 3. Periostin does not mediate intestinal inflammation in AOM/DSS models
(A) Body weight change after AOM administration. (B) Length of extracted large intestine 14 days after AOM administration. (C) Expression of inflammation-related genes in the large intestine measured by real-time PCR. (D) Histopathological score of the large intestine. Postn, Periostin.
Figure 4
Figure 4. Periostin induces apoptosis in colorectal cancer
(A) Proliferation of CMT93 cells cultured with the conditioned medium collected from Postn+/+ or Postn−/− cancer-associated fibroblasts (CAFs) (cultured for 48 h), assessed by MTT assay. *P < 0.05. (B) Proliferation of CMT93 cells under rPostn stimulation assessed by MTT assay. *P < 0.05. (C) Heatmap showing the expression profile of 20 genes in Postn-treated (Postn_1–4) and control (Control_1–4) cells, determined by microarray analysis using the weighted average difference (WAD) algorithm. Red indicates higher and green indicates lower abundance (Z-score). (D) Representative dot plots of AnnexinV and 7-AAD staining in Postn-treated or control CMT93 cells. (E) Frequency of early apoptotic cells (AnnexinV(+) and 7-AAD(–)). *P < 0.05. (F) Representative TUNEL assay images in Postn+/+ and Postn−/− mice. Bar, 50 μm. (G) Quantification of TUNEL-positive cells. n = 15. Postn, Periostin. *P < 0.05.

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