Peritoneal carcinomatosis PND-1186 frequently occurs at the later stages of gastric carcinoma, especially after surgery [2–4], which refers to the peritoneal metastatic cascade of gastric cancer and significantly contributes to gastric cancer-related mortality. To date, the mechanisms by which gastric carcinoma undergoes peritoneal carcinomatosis has not yet been specified. Stephen Paget’s ‘seed and soil’ theory of tumor metastasis may provide a clue useful for further investigation. This theory stated that the sites where metastasis occurs are defined not only by the tumor cells (seed)

but also by the local microenvironment of the metastatic site (soil) [5]. In other words, the specific site of cancer cell metastasis is not simply due to anatomic location of the primary tumor or proximity to secondary sites but rather, it involves interactions between tumor cells and the local microenvironment at the secondary site [6]. Therefore, peritoneal carcinomatosis may occur as the peritoneal stroma environment promotes tumor cells to attach to the peritoneal mesothelium by providing various growth factors and chemokines that promote tumor metastasis [7]. This process is established by the interactions between extracellular matrix associated proteins click here and signals produced by mesothelial cells and the corresponding adhesion molecules from tumor cells [8]. Extracellular matrix(ECM) that contains collagen, laminin,

fibronectin and hyaluronic acid provides ligands for b1-integrin and CD44 h and is known to participate in the peritoneal dissemination of

cancer cells [9]. Transforming growth factor-β, a family of 25 kDa homodimeric multifunctional regulatory peptides, possesses a number of biological functions, including extracellular matrix production and maturation [10]. TGF-β1 is one of the most potent fibrosis buy Napabucasin stimuli of mesothelial cells [11]; increasing evidence has suggested that why TGF-β1 can induce synthesis of extracellular matrix proteins and has been implicated as the key mediator of fibrogenesis in various tissues [12]. In our previous study, we demonstrated that the TGF-β1 level in peritoneal lavage fluid is correlated with peritoneal metastasis of gastric cancer. Other studies have shown that TGF-β1 is able to stimulate invasion and adhesion of scirrhous gastric cancer cells to the peritoneum, resulting in an increase in peritoneal dissemination of tumor cells [13–16]. However, little is known about the underlying mechanisms that regulate this activity. Adhesion polypeptides are located in the cell binding domain of ECM components, such as fibronectin, laminin, and collagen, and can bind to specific cell surface cellular adhesion molecules (CAM) known as integrins for cell-to-ECM adhesion. However, the common and characteristic RGD (Arg-Gly-Asp sequences) have been found to selectively block the binding of tumor cells to ECM, and to consequently inhibit metastasis [17].