In vivo, athymic

mice were administered thrombopoietin (TPO) to expand their megakaryocyte populations prior to intracardiac PC-3 luciferase tagged (PC-3luc) cell inoculation. TPO significantly increased MKs in the bone marrow and reduced numbers of luciferase positive prostate tumors in the long bones. These data show a novel role for megakaryocytes as potential gate-keepers in the bone marrow microenvironment of the prostate skeletal metastatic lesion. O172 Culture of Human Laryngeal Carcinoma Cell Line Hep-2 in NSC23766 Presence of Fibronectin Increases MMP-9 Expression with the Involvement of Multiple Signaling Pathways Triparna Sen1, Anindita Dutta1, Gargi Maity1, Amitava Chatterjee www.selleckchem.com/products/pnd-1186-vs-4718.html 1 1 Department of Sotrastaurin Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India The microenvironment is being increasingly recognized as critical component in tumor progression and invasion. During cell migration, there is a continuous interaction between cell surface receptors

and ECM proteins. In the present communication we studied the effect of Fibronectin-integrin interaction in human laryngeal carcinoma cell line, Hep-2 and the downstream effectors. The study indicates that culture of Hep-2 cells in SFCM in presence of FN enhances MMP-9 expression. FN induces the activity and expression of MMP-9 by binding to its receptor a5b1 in Hep-2 cells. This induction medroxyprogesterone occurs through the possible involvement of multiple signaling pathways. We propose that there is a “cross-talk” between

the signaling pathways. The silencing of FAK with FAK siRNA and its subsequent effect on FN-induced MMP-9 expression has confirmed the involvement of FAK as an important modulator in the pathway. When FN binds to its receptor, it causes the phosphorylation of FAK, which in turn causes activation and nuclear translocation of PI-3 K and subsequent activation of ERK finally leading to MMP-9 transactivation and stimulation. PI-3 K on the other hand, upon integrin ligand interaction, could also independently activate ILK. These signaling pathways work in concert with each other and disruption of one could affect the function of another. The signals from the signaling pathways finally leads to the increased DNA binding activity of important transacting factor on MMP-9 promoter and thus transcription of MMP-9 in turned on. Our study provides scopes for future clinical interventions by targeting these signaling pathways in FN-induced MMP-9 upregulation and invasion of laryngeal cancer cells.