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


METHODS
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.


CONCLUSIONS
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.
Liu
Wenli
W
Molecular and Clinical Hematology Branch, Digestive Disease Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.
Liu
Yueqin
Y
Zhu
Jianqiong
J
Wright
Elizabeth
E
Ding
Ivan
I
Rodgers
Griffin P
GP
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor