Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Pathol. 2014 Mar;184(3):859-70. doi: 10.1016/j.ajpath.2013.11.012. Epub 2014 Jan 10.

The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation.

Author information

1
Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
2
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
3
Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan.
4
Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
5
Department of Surgical Oncology, Medical School, Osaka City University, Osaka, Japan.
6
Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. Electronic address: mfukayama-tky@umin.ac.jp.

Abstract

Overexpression of periostin (POSTN), an extracellular matrix protein, has been observed in several cancers. We investigated the importance of POSTN in gastric cancer. Genome-wide gene expression analysis using publicly available microarray data sets revealed significantly high POSTN expression in cancer tissues from stage II-IV gastric cancer, compared with background normal tissues. The POSTN/vimentin mRNA expression ratio was highly associated with gene groups that regulate the cell cycle and cell proliferation. IHC showed that periglandular POSTN deposition, comprising linear deposition abutting the glandular epithelial cells in normal mucosa, disappeared during intestinal gastric cancer progression. Stromal POSTN deposition was also detected at the invasive front of intestinal-type and diffuse-type cancers. In situ hybridization confirmed POSTN mRNA in cancer-associated fibroblasts, but not in tumor cells themselves. POSTN enhanced the in vitro growth of OCUM-2MLN and OCUM-12 diffuse-type gastric cancer cell lines, accompanied by the activation of ERK. Furthermore, coinoculation of gastric cancer cells with POSTN-expressing NIH3T3 mouse fibroblast cells facilitated tumor formation. The OCUM-2MLN orthotopic inoculation model demonstrated that tumors of the gastric wall in Postn(-/-) mice were significantly smaller than those in wild-type mice. Ki-67 and p-ERK positive rates were both lower in Postn(-/-) mice. These findings suggest that POSTN produced by cancer-associated fibroblasts constitutes a growth-supportive microenvironment for gastric cancer.

PMID:
24418260
DOI:
10.1016/j.ajpath.2013.11.012
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center