The Impact Of Of Adipocytokines Derivatives On Breast Cancer Invasion And Metastasis

Obesity is a serious health problem, as it is not only associated with a variety of metabolic disorders but also with an increased risk of developing cancer. More specifically, obesity has been identified as a risk factor for breast cancer. Unfortunately, the mechanism by which obesity increases cancer risk is not yet known. Insights into the mechanism(s) through which obesity increases the risk of cancer are urgently needed to develop new strategies for the prevention and treatment of certain cancers. Current epidemiologic and experimental studies of the obesity cancer association focus on the role of increased adipose tissue, particularly the increase in circulating adipocyte-derived factors (adipokines). Multiple factors from adipose tissue, such as leptin, adiponectin, cytokines, and other secreted products, influence processes involved in carcinogenesis.Metastasis is one of the major causes of mortality in breast cancer patients and occurs as a complex multistep process that involves cancer cell adhesion, invasion, and migration. In the multiple stages of these processes, the degradation of environmental barriers, such as the extracellular matrix (ECM) and basement membrane, is the initial step, and several proteolytic enzymes participate in the degradation of these barriers. Among these enzymes, MMPs play a major role. TIMPs are natural inhibitors of MMPs found in most tissues and body fluids. By inhibiting MMPs activities, they participate in tissue remodeling of the ECM and inhibit tumor invasion and metastasis. Numerous investigations have pointed out that the MMPs and TIMPs play an important role in the invasion and metastasis of cancers. In addition, MMP-2 and MMP-9 degrade components of the basement membrane and are strongly implicated in the invasion and metastasis of malignant tumors. Therefore, the inhibition of invasion mediated by MMP-2 and MMP-9 may be crucial for the inhibition of cancer metastasis. Recent clinical studies have shown that MMP activity is required for rapidly proliferating and invading tumors rather than for already established tumors. Thus, the inhibition of MMP activity is important for the prevention of early stage carcinogenesis, particularly the tumor promotion process.Resistin is known as an adipocyte-specific secretory cysteine-rich hormone that can cause insulin resistance and decrease adipocyte differentiation. Many aspects studies have provided evidence of a role of resistin in inflammatory processes that may be involved in atherosclerosis. The aim of this study was to elucidate the potential of resistin-13-peptide as an inhibitor of MMP-2 and MMP-9 activities using gelatin zymography, and to present the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 proteins using western blotting. We also investigated the influence of resistin-13-peptide on cancer cell viability, colony formation, adhesion, invasion, and animal experiment using MDA-MB-231 breast cancer cells. In results, Resistin-13-peptide inhibited MDA-MB-231 cells growth and colony formation in dose-dependent and time-dependent manners. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by resistin-13-peptide in dose-dependent manners. Resistin-13-peptide decreased the gelatinolytic activities of both MMP-2 and MMP-9, enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA- MB-231 cells. The animal experiments found the growth of tumors were repressed by resistin-13- peptide, which not injured other organs in the same time. Especially ovaries didn't have pathological changes yet. In conclusions, the treatment with resistin-13- peptide is effective in suppressing tumor proliferation, adhesion and invasion. The possible mechanism is down-regulation of MMPs and up-regulation of TIMPs.In addition, adiponectin, a major adipose cytokine, plays a crucial role in the inhibition of metabolic syndrome by acting on such cell types as muscle cells and hepatocytes. Furthermore, evidence suggests that adiponectin may influence cancer pathogenesis. Previous studies have been reported on the potential link between breast cancer and adiponectin in the epidemiologic surveys. Low serum adiponectin levels may be a novel risk factor for breast cancer and study of adiponectin biology can provide new insights into the association of obesity with cancer risk. Since the mechanisms of action of adiponectin are not entirely clear, future studies are needed to fully elucidate the action of this hormone. In the present study, we investigated the influence of g-adiponectin, which is human adiponectin globular domain (104-247) recombinant protein, on cancer cell viability, adhesion, invasion and motility using MDA-MB-231 cells. Furthermore, we determined the potential effects of g-adiponectin on MMP-2 and MMP-9 activities using gelatin zymography, and to present the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 proteins and mRNA using western blotting and RT-PCR assays. In results, adiponectin recombinant inhibited MDA- MB-231 cells growth and colony formation in dose-dependent and time-dependent manners. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by adiponectin recombinant in dose-dependent manners. Adiponectin recombinant decreased the gelatinolytic activities of both MMP-2 and MMP-9, enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA- MB-231 cells. This was testified in mRNA level in the same time. In conclusions, the treatment with adiponectin recombinant is effective in suppressing tumor proliferation, adhesion and invasion. The possible mechanism is down-regulation of MMPs and up-regulation of TIMPs.