The Relationship Of Intgrin α V β 6 And Cancer Associated Fibroblasts With Biological Behavior In Malignant Tumor

BackgroundIntegrin is a kind of receptor protein located in cell membranes which active some signaling between cells and cells, or cells and external environments. Integrin is one of the family members on the cellular surface receptor, whose expression could regulate the function of cellular adhesion, more over it could be taking supported, pulled and/or fixed to the cell movement. Previous research shows that integrin beta 6 plays an important role as a member of the integrin subunit familys. The subunit of integrin beta 6 is proofed to be only connected with the subunit of alpha V as a key molecule which participated in the growth of tumor development. In normal organism physiological structure, integrin alpha V beta 6 also plays an important role to adjuct normal functions, such as some other benign lesions case of tissue injuries and inflammation processes, which is proofed that integrin alpha V beta 6 could achieve the efforts of helping organize rebuilding. The high expressions of integrin alpha V beta 6 in normal tissue could promote epithelial cell proliferation and migration to repair and be instead of the injuried epithelial tissue. While in some epithelial tumors and other cancer cell lines, integrin alpha V beta 6 also can be measured with a high expression level compared with normal tissue. Many malignant cells are closely related with the expression of various subtypes of integrin family. The expressions of integrin alpha V beta 6 have been confirmed there are associated with tumor invasion, metastasis and other mechanisms in colon cancer cells. This function of integrin subunit structure is closely related with malignant tumors, promoting tumor progression. As a kind of cellular adhesive molecular receptor, integrin alpha beta 6 V plays an important function in a variety of the invasion and metastasis of malignant tumor. The abnormal expressions of integrin subunit alpha 2 are widely found in completely undifferentiated carcinomas, and the abnormal expression of integrin alpha 6 have recently been found in some malignant tumors. Integrin beta 6 promote the invasion and metastasis of malignant tumor as a kind of cellular adhesive molecular receptors. Integrin beta 6 is considered as an important intermediary factor to activate tumor growth. Therefore, aim of this study attempts to prove the function of integrin beta 6 in tumor proliferation, survival, invasion and metastasis.Cancer associated fibroblasts (CAFs) is known as a kind of activated fibroblast cells located in the tumor microenvironment, and it is an important structure of the tumor stroma cells. It is very important of the function on cancer associated fibroblasts which interact with tumor cells to promote tumor growth and progression in microenvironment. The invasion and metastasis of tumor cell actually is a multi-stage process, in which the cell adhesion seems to be an important role. Thus many reseaches target those factors associated with cell adhesion and these factors have became research hotspot in these years. Cancer associated fibroblasts can express the smooth muscle cell markers of alpha smooth muscle actin (alpha SMA), which is relation with some growth factors and cytokines to promote the growth of tumor cells and angiogenesis. Previous studies have found that integrin proteins are high expressions in tumor cells; some subunits of integrin can effect the growth of fibroblasts by the interaction of alpha SMA and integrin in tumor tissue. In vitro cancer cell experiments, studies have confirmed that the expressions of alpha SMA in cancer associated fibroblasts are lower integrin alpha 3 be knocking down by shRNA in tumor cells. Thus, the expression levels of integrin alpha V 6 subunits and alpha SMA may be one of the important indications for the development of metastatic disease as the evaluation of the patient prognosis with a high-risk gastric cancer. MMP-2 and MMP-9 are other important factors which are relation with tumor cells, invasion and metastasis. Previous research, we found that the inhibition of integrin beta 6 could downregulate the expressions of phosphorylation and/or non phosphorylated ERK1/2, which inhibit uPA secretion in tumor cell culture, pro MMP-9 and pro-MMP-2.Part one Clinical Significance of Integrin αvβ6 Expression effects on Gastric Carcinoma Invasiveness and Progression via Cancer-associated FibroblastsABSTRACTBackground. Over-expression of integrin αvβ6 and increased numbers of cancer-associated fibroblasts (CAFs) play an important role in the development and progression of cancers.Methods. The aim of this study is to investigate the expression level of integrin αvβ6 and CAF numbers, their correlation with clinicopathologic features, and their role in the prognosis of human gastric cancers.Results. The expression levels of integrin αvβ6 and a-SMA in CAFs were analyzed by immunohistochemistry. Their correlation with clinicopathologic features, the relationships and the survival time of patients were also analyzed. The integrin αvβ6 expression levels were analyzed mainly in gastric cancers. The α-SMA expression levels were analyzed mainly in gastric cancers and paraneoplastic tissues. Patients with positive integrin β6 and α-SMA expression have a significantly lower overall survival rate than those with negative integrin β6 and α-SMA expression (P<0.05). A multivariate analysis using a log-rank test indicated that patients with positive integrin β6 and α-SMA expression and/or a diffuse type of gastric cancer had a significantly poorer overall survival rate than did those with negative integrin β6 expression (P<0.05).Conclusions. Integrin β6 expression correlated significantly with CAF numbers and served as a valuable prognostic indicator for human gastric cancers.Part two Clinical Significance of Integrin β6 as a Tumor Recurrence Factor in Follicular Thyroid CarcinomaABSTRACTBackground. Over-expression of integrin β6 plays an important role in a variety of malignant tumor invasion and metastasis.Methods. The expression levels of integrin β6, MMP-2 and MMP-9 were analyzed by immunohistochemistry with human follicular thyroid carcinomas. Then we investigated their correlation with clinical outcomes parameters, relationship and the survival time.Results. The integrin β6 staining was observed in cellular membrane and cytoplasm of follicular thyroid carcinoma cells. The MMP-2 and MMP-9 expressions were mainly found in cellular cytoplasm. In correlation with the clinical outcome parameters of 60 patients, there were significant statistical differences of integrin β6, MMP-2 and MMP-9 expression levels in different sizes of tumor. Integrin β6 and MMP-9 expressions have significant statistical differences in different T classifications. MMP-2 and MMP-9 expressions have significant statistical differences in different M classifications. Other clinical outcome parameters had no significant statistical differences.Conclusions. Integrin β6 expression correlated significantly with MMP-9 expression, and may be a valuable recurrence indicator for follicular thyroid carcinomas.