Relationship Of TGF-β1 And Smad4 Expression With Angiogenesis In Human Colorectal Tumor

Background and objectives: Colorectal carcinoma is one of the common malignant tumors that its incidence rate and death rate both rank the forefront of all the malignant tumors. As other tumors, colorectal carcinoma also has characteristics such as invasion and metastasis in process of its occurrence and development, but the mechanism is not fully understood. Recent studies have showed that secretive disorders and signaling pathway disturbance of transforming growth factor (TGF- ) are closely related to the progression and aggressiveness of malignant tumors.TGF- signal transduction is involved in fundamental biological processes, such as cell growth regulation, differentiation, adhension, the formation of extracellullar matrix (ECM), immune regulation and cell apoptosis. Recent progress has led to the elucidation of a general TGF- B signal pathway: Firstly, TGF- ligand adheres to transforming growth factor B receptor I , II (T B R I ,T R II) and T R I is phosphorylated by T B RII. Then, Smad2 and Smad3 are activated by T B R I and form heteromeric complexes with Smad4. These complexes translocate to the nucleus where they control expression of target genes. TGF- B 1 is a major member of TGF- B family and it expresses a high level in many tumor tissues, but its mechanism is not clear. Smad4, a new anti-oncogene, plays a key role in TGF- B signal transduction and express a low level in many human tumor tissues. The disorders of TGF- B signal transduction are always closely to the invasion and metastasis of tumors.Researches have indicated that the growth of tumor is dependent on angiogenesis.Angiogenesis of tumors plays an important role in tumor cells' invasion and metastasis. Microvessel density (MVD) is quantitative indicator of angiogenesis. In addition, angiogenesis is also mediated by proto-oncogene, anti-oncogene and some growth factors. Studies have showed that TGF- P 1 plays an important role in angiogenesis of many tumors while Smad4 is an inhibitor of angiogenesis, but there exist lots of differences in colorectal carcinoma. In order to investigate the possible mechanism of colorectal carcinoma , an immunohistochemical streptavidin-peroxidase (SP) method was used to exmine the expression of TGF- P 1 , Smad4 and MVD in colorectal carcinoma and the correlation between these three proteins.Materials and methods: (1) 64 surgically resected carcinoma of colorectal carcinoma samples, 24 adenoma samples and 1 0 normal mocosa samples of colorectal carcinoma which were adjacent to carcinoma mucosa, were confirmed pathologically. All the tissues were fixed in 10% neutral formalin and embedden in paraffin. (2) SP immunohistochemical staining technique was used to exmine the expression of TGF- P 1 , Smad4 and CD34 in normal mucosa, adenoma and colorectal carcinoma. (3) The datawere analyzed by software SPSS 10.0. x -test or t-test was used to analysize the difference between different groups. P value < 0.05 was considered as statistically significant.Results: (1) TGF- P 1 protein was stained mainly in the cytoplasm of cells .Normal epithelial cells and adenoma were homogeneously stained by TGF- P 1 , whereas the positive tumor cells were heterogeneously distributed within colorectal carcinoma. Smad4 protein was stained mainly in the cytoplasm of cells, and occasionally evident in membrane of cells. CD34 protein was stained mainly in the cytoplasm of vascular endothelial cells. The positive rates of TGF- P 1 in colorectal carcinoma group, colorectal adenoma group and normal mocosa group were 70.31%, 33.33% and 30% respectively. There were significant differences (P<0.05) between normal mocosa group or adenoma group and carcinoma group, but no differences were observed between normal mocosa group and adenoma group. The positive rates of Smad4 in colorectal carcinoma group, colorectal adenoma group and normal mocosa group were 46.88%, 83.33% and 90% respectively. There were significant differences (P<0.05) betweennormal mocosa group or adenoma group and carcinoma group, but no significance differ...