Reduced hGC-1 protein expression is associated with malignant progression of colon carcinoma

Clin Cancer Res. 2008 Feb 15;14(4):1041-9. doi: 10.1158/1078-0432.CCR-07-4125.

Abstract

Purpose: hGC-1 (human granulocyte colony-stimulating factor-stimulated clone 1) is a gastrointestinal protein that is a member of the olfactomedin glycoprotein family. Its biological function remains poorly understood. Aberrant expression of hGC-1 in some human carcinomas has been recently reported. The purpose of this study was to examine hGC-1 expression in colon carcinoma and explore the relationship between hGC-1 expression and the clinicopathologic features of patients with colon cancer.

Experimental design: The expression of hGC-1 in colon adenocarcinoma tissues was examined by dot-blot analysis, in situ hybridization, and immunohistochemistry. The association of hGC-1 expression pattern with patient differentiation grade, tumor stage, metastasis, and survival were examined. To further investigate the involvement of hGC-1 in colon cancer progression, human colon carcinoma (HT-29) cells overexpressing hGC-1 were established and cell proliferation, adhesion, and migration were studied.

Results: Compared with normal colon mucosa, the up-regulation of hGC-1 was more frequently detected in more differentiated colon cancers, whereas down-regulation or no expression was associated with poorly differentiated colon cancers. Interestingly, hGC-1 down-regulation was also found in late tumor-node-metastasis stage, metastasis, and in patients with shorter survival. The morphology and cortical actin distribution of HT-29 cells were altered by hGC-1 overexpression. However, this did not change cell proliferation, but decreased cell adhesion and migration.

Conclusion: Our findings indicate that hGC-1 is involved in colon cancer adhesion and metastasis, and that hGC-1 may be a useful marker for tumor differentiation and progression of human colon carcinoma.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • DNA Methylation
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Gene Expression
  • Granulocyte Colony-Stimulating Factor / biosynthesis*
  • Granulocyte Colony-Stimulating Factor / genetics
  • HT29 Cells
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Granulocyte Colony-Stimulating Factor