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Reduced hGC-1 Protein Expression Is Associated with Malignant Progression of Colon Carcinoma

Authors' Affiliations: ¹ Molecular and Clinical Hematology Branch, ² Digestive Disease Branch, ³ Office of the Director, National Institute of Diabetes, Digestive, and Kidney Diseases, and ⁴ Organ System Branch, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Griffin P. Rodgers, Molecular and Clinical Hematology Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, NIH, Building 10, Room 9N119, 9000 Rockville Pike, Bethesda, MD 20892. Phone: 301-402-2418; Fax: 301-480-1940; E-mail: gr5n{at}nih.gov.

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.