Moreover, CRF peptides and their receptors are also present in the immune system and possess immu nomodulatory properties. Peptides of the CRF family and their receptors have been detected in various tumors. Several neuroendocrine tumor cell lines such as the PC12 pheochromocytoma, Y79 retinoblastoma, IMR 32 and concerning SH SY5Y neuroblast oma, AtT 20 pituitary carcinoma and NCI H82 small cell lung cancer cell lines express CRF and the CRF1 receptor. In addition, epithelial tumors and epithelial tumor cell lines express CRF receptors. CRF1 receptors have been detected in the MCF7 breast cancer cell line, while CRF immunoreactivity has been reported in surgical breast cancer specimen, suggesting a role for the CRF/CRF receptor system in breast cancer. CRF and its recep tors are also expressed in human melanomas and in melanoma cell lines.

It should be noted here that CRF is constantly present in the microenvironment of tumors produced by nearby cells including endothelial cells and immune cells and by the local neuronal innervations. A number of reports support both a tumor promoting Inhibitors,Modulators,Libraries and a tumor inhibitory effect of CRF peptides. Thus, in the endometrial adenocarcinoma cell line Ishikawa Inhibitors,Modulators,Libraries UCN and CRF inhibit cell proliferation via CRF1. UCN was also shown to inhibit the proliferation of melanoma cells both in vitro and Inhibitors,Modulators,Libraries in vivo, through CRF1. In the human breast cancer cell line MCF7, CRF inhibits estrogen induced proliferation via CRF1. Moreover, CRF and CRF related peptides, sauvagine and UCN, inhibit the pro liferation of human HaCaT keratinocytes via CRF1.

In addition, CRF has been found to induce the expression of Fas ligand and apoptosis in the rat PC12 pheochromo cytoma cell line also via CRF1. In contrast, in the Y79 retinoblastoma cell line CRF suppresses apoptosis via downregulation of pro caspase 3 cleavage and activation. It should be mentioned here that the tumor promot ing properties for CRF can be supported Inhibitors,Modulators,Libraries by the fact that CRF induces Fas ligand production in ovarian cancers, an effect resulting in cytotoxic T cell apoptosis and local immunosuppression. Interestingly, ligands of the other CRF receptor, the CRF2, have been found to sup press tumor growth while the expression of the CRF2 spe cific endogenous ligand UCN2 in tumors results in reduced angiogenesis and suppression of tumor growth.

Even though expression of CRF and its receptors has been described in different Inhibitors,Modulators,Libraries types of cancer cells, the role of these peptides in tumor growth and metastasis has not been elucidated. The aim of this work http://www.selleckchem.com/products/Belinostat.html was to study the role of CRF in breast cancer cell homeostasis, motility and invasiveness. For this purpose we utilized the MCF7 breast cancer cell line and found that while CRF affected apopto sis it also promoted cell motility and invasiveness, sup porting a tumor promoting role for CRF and CRF1 signals.