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Complex Molecular Interactions (complex + molecular_interaction)
Selected AbstractsExtracellular and intracellular mechanisms that mediate the metastatic activity of exogenous osteopontinCANCER, Issue 8 2009Jami Mandelin PhD Abstract BACKGROUND: Osteopontin affects several steps of the metastatic cascade. Despite direct correlation with metastasis in experimental systems and in patient studies, the extracellular and intracellular basis for these observations remains unsolved. In this study, the authors used human melanoma and sarcoma cell lines to evaluate the effects of soluble osteopontin on metastasis. METHODS: Exogenous osteopontin or negative controls, including a site-directed mutant osteopontin, were used in functional assays in vitro, ex vivo, and in vivo that were designed to test the extracellular and intracellular mechanisms involved in experimental metastasis. RESULTS: In the extracellular environment, the results confirmed that soluble osteopontin is required for its prometastatic effects; this phenomenon is specific, arginine-glycine-aspartic acid (RGD)-dependent, and evident in experimental models of metastasis. In the intracellular environment, osteopontin initially induced rapid tyrosine 418 (Tyr-418) dephosphorylation of the cellular homolog of the Rous sarcoma virus (c-Src), with decreases in actin stress fibers and increased binding to the vascular endothelium. This heretofore undescribed Tyr dephosphorylation was followed by a tandem c-Src phosphorylation after tumor cell attachment to the metastatic site. CONCLUSIONS: The results of this study revealed a complex molecular interaction as well as a dual role for osteopontin in metastasis that depends on whether tumor cells are in circulation or attached. Such context-dependent functional insights may contribute to antimetastasis strategies. Cancer 2009. © 2009 American Cancer Society. [source] Signaling in the third dimension: The peripodial epithelium in eye disc developmentDEVELOPMENTAL DYNAMICS, Issue 9 2009Mardelle Atkins Abstract The eye-antennal imaginal disc of Drosophila melanogaster has often been described as an epithelial monolayer with complex signaling events playing out in two dimensions. However, the imaginal disc actually comprises two opposing epithelia (the peripodial epithelium, or PE, and the disc proper, or DP) separated by a lumen to form a sac-like structure. Recent studies expose complex molecular interactions between the PE and the DP, and reveal dynamic communication between the two tissues. Further findings suggest the PE makes important contributions to DP development by acting as a source of signaling molecules as well as cells. Here we summarize those findings and highlight implications for further research. Developmental Dynamics 238:2139,2148, 2009. © 2009 Wiley-Liss, Inc. [source] Patterning the limb before and after SHH signallingJOURNAL OF ANATOMY, Issue 1 2003Lia Panman Abstract The vertebrate limb is one of the most relevant experimental models for analysing cell,cell signalling during patterning of embryonic fields and organogenesis. Recently, the combination of molecular and genetic studies with experimental manipulation of developing limb buds has significantly advanced our understanding of the complex molecular interactions co-ordinating limb bud outgrowth and patterning. Some of these studies have shown that there is a need to revise some of the textbook views of vertebrate limb development. In this review, we discuss how signalling by the polarizing region is established and how limb bud morphogenesis is controlled by both long-range and signal relay mechanisms. We also discuss recent results showing that differential mesenchymal responsiveness to SHH signalling is established prior to its expression by the polarizing region. [source] Transforming growth factor-, signaling at the tumor,bone interface promotes mammary tumor growth and osteoclast activationCANCER SCIENCE, Issue 1 2009Mitsuru Futakuchi Understanding the cellular and molecular changes in the bone microenvironment is important for developing novel therapeutics to control breast cancer bone metastasis. Although the underlying mechanism(s) of bone metastasis has been the focus of intense investigation, relatively little is known about complex molecular interactions between malignant cells and bone stroma. Using a murine syngeneic model that mimics osteolytic changes associated with human breast cancer, we examined the role of tumor,bone interaction in tumor-induced osteolysis and malignant growth in the bone microenvironment. We identified transforming growth factor-, receptor 1 (TGF-,RI) as a commonly upregulated gene at the tumor-bone (TB) interface. Moreover, TGF-,RI expression and activation, analyzed by nuclear localization of phospho-Smad2, was higher in tumor cells and osteoclasts at the TB interface as compared to the tumor-alone area. Furthermore, attenuation of TGF-, activity by neutralizing antibody to TGF-, or TGF-,RI kinase inhibitor reduced mammary tumor-induced osteolysis, TGF-,RI expression and its activation. In addition, we demonstrate a potential role of TGF-, as an important modifier of receptor activator of NF-,B ligand (RANKL)-dependent osteoclast activation and osteolysis. Together, these studies demonstrate that inhibition of TGF-,RI signaling at the TB interface will be a therapeutic target in the treatment of breast cancer-induced osteolysis. (Cancer Sci 2009; 100: 71,81) [source] | |||||||||||||