Periostin Is Expressed in Pericryptal Fibroblasts and Cancer-associated Fibroblasts in the Colon

Abstract

S U M M A R Y Periostin is a unique extracellular matrix protein, deposition of which is enhanced by mechanical stress and the tissue repair process. Its significance in normal and neoplastic colon has not been fully clarified yet. Using immunohistochemistry and immunoelectron microscopy with a highly specific monoclonal antibody, periostin deposition was observed in close proximity to pericryptal fibroblasts of colonic crypts. The 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 cancerassociated fibroblasts. ISH showed periostin signals in cancer-associated fibroblasts but not in cancer cells. Ki-67-positive epithelial cells were significantly decreased in the colonic crypts of periostin 2/2 mice (?0.6-fold) compared with periostin 1/1 mice. In three-dimensional coculture within type I collagen gel, both colony size and number of human colon cancer cell line HCT116 cells were significantly larger (?1.5-fold) when cultured with fibroblasts derived from periostin 1/1 mice or periostin-transfected NIH3T3 cells than with those from periostin 2/2 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. (J Histochem Cytochem 56:753-764, 2008)

Circulating levels of periostin may help identify patients with more aggressive colorectal cancer

“…The expression of periostin has been shown to play a role in colon cancer progression by influencing cell growth, invasion, and apoptosis (7,23,24). In the present study, we investigated both serum levels and expression of periostin in CRC tissue samples, and analyzed potential correlations between serum periostin levels and certain clinical characteristics of the tumor.…”

Role of periostin in esophageal, gastric and colon cancer

“…Kikuchi et al (31) identified the connection between periostin expression and colorectal crypt fibroblasts and infiltrating fibroblasts of the tumor tissue. Periostin-mediated induction of fibroblasts resulted in an increase in the number of HCT 116 colon cancer cells in co-culture (31).…”

Roles of epithelial cell-derived periostin in TGF-β activation, collagen production, and collagen gel elasticity in asthma

“…Full-length periostin is a secreted 90-kDa disulfide-linked protein composed of a typical signal sequence followed by a cysteine-rich EMI domain (believed to be important in multimerization), a tandem repeat of four fascilin-like (FAS1) domains-an evolutionarily conserved domain considered important in adhesion-and a variable C-terminal region (2)(3)(4)(5). Periostin is considered a matricellular protein with expression confined to cells in connective tissues, including the periodontal ligament, tendons, heart valves, myocardium, skin, and bone (6,7). Despite lacking an RGD domain, periostin is thought to interact with multiple integrins, including αVβ3, αVβ5, and α6β4, to initiate a variety of biologic effects including cell proliferation, cell migration, epithelial to mesenchymal transformation, modulation of the biomechanical properties of connective tissues, and regeneration of cardiac myocytes after injury (4,8,9).…”