Periostin Is Expressed in Pericryptal Fibroblasts and Cancer-associated Fibroblasts in the Colon
Yoshinao Kikuchi 1, Takeshi G. Kashima 1, Takashi Nishiyama 1, Kazuhiro Shimazu 1, Yasuyuki Morishita 1, Masashi Shimazaki 1, Isao Kii 1, Hisanaga Horie 1, Hideo Nagai 1, Akira Kudo 1 and Masashi Fukayama 1*
1 Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan (YK,TGK,KS,YM,MF); Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan (TN,MS,IK,AK); Department of Surgery, Jichi Medical School, Tochigi, Japan (HH,HN); and Ibaraki Prefectural Central Hospital, Ibaraki, Japan (HN)
* To whom correspondence should be addressed. E-mail: mfukayama-tky{at}umin.ac.jp.
Submitted on February 4, 2008
Accepted on 15 April 2008
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Abstract |
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Periostin is a unique extracellular matrix protein, deposition of which is enhanced by mechanical stress and tissue repair process. Its significance in normal and neoplastic colon has not been fully clarified yet. Using immunohistochemistry and immuno-electron microscopy with a highly specific monoclonal antibody, periostin deposition was observed in close proximity to pericryptal fibroblasts of colonic crypts. Pericryptal pattern of periostin deposition was decreased in adenoma and adenocarcinoma, preceding the decrease of the number of pericryptal fibroblasts. Periostin immunoreactivity appeared again at the invasive front of the carcinoma and increased along the appearance of cancer-associated fibroblasts. In situ hybridization demonstrated periostin signals in the cancer-associated fibroblasts, but not in the cancer cells. Ki-67 positive epithelial cells were significantly decreased in the colonic crypts of periostin-/- mice (~0.6 fold), compared to periostin+/+ mice. In three-dimensional co-culture within type I collagen gel, both colony size and number of human colon cancer cell line, HCT116 were significantly larger (~1.5 fold) when cultured with fibroblasts derived from periostin+/+ mice or periostin-transfected NIH3T3 cells than with those from periostin-/- mice or periostin non-producing NIH3T3 cells, respectively. Periostin is secreted by pericryptal and cancer-associated fibroblasts in the colon, both of which support the growth of epithelial components.
Key Words:
periostin, pericryptal fibroblast, cancer-associated fibroblast, colon, adenoma-carcinoma sequence
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