1. Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers
- Author
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Tsuyoshi Fukushima, Hiroaki Kataoka, Shuichiro Uchiyama, Koki Nagaike, Hiroyuki Tanaka, Seiji Naganuma, Kazuo Chijiiwa, Hiroshi Itoh, and Ryouichi Hamasuna
- Subjects
Adenoma ,Pathology ,medicine.medical_specialty ,Cellular differentiation ,Cell Count ,CHO Cells ,Adenocarcinoma ,Biology ,Gastrointestinal epithelium ,Cricetulus ,Cell Line, Tumor ,Cricetinae ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Nuclear protein ,Lymph node ,In Situ Hybridization ,beta Catenin ,Colorectal Cancer ,Hyperplasia ,Gastroenterology ,Intestinal Polyps ,Nuclear Proteins ,Cell Differentiation ,Epithelial Cells ,medicine.disease ,Immunohistochemistry ,Epithelium ,Neoplasm Proteins ,Intestines ,medicine.anatomical_structure ,Lymphatic Metastasis ,Colonic Neoplasms ,Cancer cell ,Cancer research ,Colitis, Ulcerative ,Hepatocyte growth factor ,Colorectal Neoplasms ,Cell Division ,Transcription Factors ,medicine.drug - Abstract
Background: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. Aims: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. Methods: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. Results: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear β-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. Conclusion: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers. more...
- Published
- 2007
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