| Background: Currently, breast cancer is one of the most common malignancy in women worldwide,accounting for 40% of female cancer. Transfer is an important cause of death in patients with breast cancer.Breast cancer will violate and undermine the normal breast tissue of women at the lymphatic and then through blood tract, causing local or systemic recurrence. In addition, parts of the breast adipose tissue is the main one of the components before the adipose tissue is simply understanding become an energy-storing tissue, but in recent years the study of adipose adipocytes and their secretory products, it is no longer just is considered to be substantially inert energy storage cells, a variety of factors secreted by adipocytes will be involved in the development of breast cancer, invasion and metastasis. Currently found in human adipocytes can secrete more polypeptides of about 100 substances, including vascular endothelial growth factor(vascular endothelial growth factor, VEGF), hepatocyte growth factor(hepatocyte growth factor, HGF), leptin(Leptin, LP), tumor necrosis factor(tumor necrosis factor-alpha, TN Fa),heparin-binding epidermal growth factor-like growth factor(heparin-binding epidermal growth factor-like growth factor, HBEGF), interleukin-6(IL-6), etc., known as adipokines(adipocytokines). These fats cytokines may be an important factor leading to the deterioration of breast cancer. So explore the molecular mechanisms of interactions between breast cancer and adipocytes, finding an effective intervention strategy has a very important significance.Cancer immunotherapy is by mobilizing the body's immune system by enhancing the body's anti-tumor immunity, inhibit and kill tumor cells. Cancer immunotherapy is currently one of the areas of cancer treatment in the most promising research directions. As we all know, activated T cells need to "double signal" of intervention, namely histocompatibility complex(MHC)- peptide-T-cell antigen receptor T cell antigen receptor(TCR) complex as the first signal and antigen presenting cells(APC) second costimulatory signal(ie, the auxiliary signal) molecule provided, when the body is missing costimulatory molecules when stimulated cause imbalance response of T cells, making tumors escape immune surveillance. PD-1 as one of the co-stimulatory molecule family members, plays a very important role in T, B cell activation. Thus,PD-1 as a target for immune regulation has important significance in anti-tumor therapy.Methods: In this study, animal experiments, we isolated in childhood B / C female mice inguinal adipose tissue of one fibroblast-like cells, called adipose stem cells(ADSCs), which induced to mature fat cell. We will adipocytes and breast cancer cells were co-cultured using western blot, immunohistochemistry,real-time quantitative PCR method is relatively independent culture and subsequent breast cancer 4T1 cellsand expression of protein and mRNA levels EMT6 PD-L1 co-culture. We mice were divided into two groups AB, A group of adipocytes and breast cancer cells(3: 1) mixed inoculated subcutaneously, group B individual breast cancer cells were inoculated subcutaneously compared two groups of mice tumor and tumor size of speed.Studies have clarified STAT3 signaling pathway and the Notch signaling pathway and some types of cancer, transformation, closely related to the invasion and metastasis. We found that inflammatory cytokines IL-1?, TNF-? and IL-6, etc. either directly or indirectly activated STAT3 signal of tumor cells to induce EMT and CSC conversion. Through real-time quantitative RT-PCR and ELISA test and Western blot method to detect adipocytes co-cultured with breast cancer cells, STAT3 phosphorylation levels and inflammatory cytokines IL-1?, TNF-? and IL-6, etc. expression.Results: The mRNA and protein levels, after co-cultured 4T1 breast cancer cells cultured alone and compared to EMT6 cells capable of high expression of PD-L1. Since the PD-1 / PD-L1 is expressed on the surface of a variety of tumors co-suppression molecule that plays an important role in breast tumor cells mediating immune escape. Through animal experiments found that adipocytes and breast cancer cells(3: 1)mixed subcutaneously in vivo tumor faster, and are more prone to lung cancer metastasis. These results indicate that breast cancer cells under the effect of adipocytes, its migration, invasion, metastasis and tumorigenicity significantly enhanced immunogenicity. It showed that adipocytes treated breast cancer cells acquire malignant phenotype.At the same time we found results with adipocytes co-cultured breast cancer cells, STAT3 phosphorylation levels were significantly increased, the expression of Notch cut body is increased. After co-cultured adipocytes in IL-6 mRNA expression levels increased more than tenfold, and, STAT3 inhibitor partially reversed adipocytes co-cultured with breast cancer cells caused by increased expression of PD-L1 phenomenon. This suggests that activation of IL-6 / STAT3 signaling axis in breast cancer cells PD-L1 played an important role in the process of overexpression.Conclusion:(1)Adipocytes can promote breast cancer cells expressing high PD-L1, so that the tumor immune escape.(2) Adipocytes through activation of IL-6 / STAT3 signaling axis causes breast cancer cells acquire malignant phenotype and immune escape. |
PDF Full Text Request