We have cloned a novel hematopoietic granulocyte colony-stimulating factor (G-CSF)-induced olfactomedin-related glycoprotein, termed hGC-1 (human G-CSF-stimulated clone-1). mRNA differential display was used in conjunction with a modified two-phase liquid culture system. The hGC-1 gene encodes a 510-amino acid glycoprotein whose exact in vivo localization and function still remains elusive. A recent study showed that hGC-1 mRNA expression is upregulated in gastric caner. To further explore a potential relationship between hGC-1 and gastric carcinoma, we investigated the expression pattern of hGC-1 protein in 173 cases of gastric carcinoma. Using immunohistochemistry, we demonstrated that hGC-1 is expressed in the esophagus, stomach, small intestine and colon. We demonstrated a striking correlation between hGC-1 expression and the histological type and differentiation grades of gastric carcinoma. Enhanced hGC-1 expression is more frequently seen in intestinal- type adenocarcinoma, while loss of expression tends to occur in the diffuse-type. hGC-1 is highly expressed in well or moderately differentiated cancer tissues and remarkably reduced or lost in poorly differentiated or undifferentiated tissues. We have subsequently examined the hGC-1 expression in colon carcinoma and explore the relationship between hGC-1 expression and clinico-pathological features of colon cancer patients. The expression of hGC-1 in colon adenocarcinoma tissues was examined by dot-blot analysis, in situ hybridization and immunohistochemistry. Compared to normal colon mucosa, upregulation of hGC-1 was more frequently detected in more differentiated colon cancers, while downregulation or no expression was associated with poorly differentiated colon cancers. Interestingly, hGC-1 downregulation was also found in late tumor-node-metastasis (TNM) stage, metastasis, and patients with shorter survival. To investigate the involvement of hGC-1 in colon cancer progression, human colon carcinoma (HT-29) cells overexpressing hGC-1 were established. The morphology and cortical actin distribution of HT-29 cells were altered by hGC-1 over-expression. However, this did not change cell proliferation, but decreased cell adhesion and migration. 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.These investigations define for the first time the expression pattern of hGC-1 in the normal human gastrointestinal tract and provide a novel and sensitive marker for the differentiation of gastric carcinoma. ? ? Because these findings implicate a role of hGC-1 in tumorgenesis, and because hGC-1 is located on chromosome 13q14.1, near a site of a putative prostate cancer tumor suppressor gene, we examined the role of hGC-1 in prostate carcinogenesis. Higher grade and metastasis of prostate cancer are mainly cause death of prostate cancer patients. RNA expression of hGC-1 was detected in the normal prostate however the expression of hGC-1 protein have not examined. We have done an immunohistochemistry staining with hGC-1 antibody and stained 18 normal prostate specimens and 159 different grades of prostate cancer specimens. We have found that lower or lost expression of hGC-1 are significantly associated with higher Gleason score of prostate cancer specimens. hGC-1 was not detected in PC-3, LNCap and Du145 cells that derived from metastasized prostate cancer. Furthermore, we compared the expression of hGC-1 to prostate specific antigen (PSA) and E-cadherin by immunohistochemistry staining with series cutting prostate cancer tissue arrays containing 112 specimens. The results indicated that expressed pattern of hGC-1 are most correlated with the expression of E-cadherin (P<0.001) and less correlated with PSA (P<0.004).
| Liu, W; Zhu, J; Cao, L et al. (2007) Expression of hGC-1 is correlated with differentiation of gastric carcinoma. Histopathology 51:157-65 |
| Liu, Wenli; Chen, Ling; Zhu, Jianchong et al. (2006) The glycoprotein hGC-1 binds to cadherin and lectins. Exp Cell Res 312:1785-97 |
| Zhuang, Zhengping; Huang, Steve; Kowalak, Jeff A et al. (2006) From tissue phenotype to proteotype: sensitive protein identification in microdissected tumor tissue. Int J Oncol 28:103-10 |
| Zhang, Jiachang; Liu, Wen Li; Tang, Delia C et al. (2002) Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development. Gene 283:83-93 |
