Loss of ADAM9 Leads to Modifications of the Extracellular Matrix Modulating Tumor Growth.

ADAM9 is a metalloproteinase strongly expressed at the tumor-stroma border by both tumor and stromal cells. We previously showed that the host deletion of ADAM9 leads to enhanced growth of grafted B16F1 melanoma cells by a mechanism mediated by TIMP1 and the TNF-α/sTNFR1 pathway. This study aimed to dissect the structural modifications in the tumor microenvironment due to the stromal expression of ADAM9 during melanoma progression.

Connectivity maps for biosimilar drug discovery in venoms: the case of Gila monster venom and the anti-diabetes drug Byetta®.

Like most natural product libraries animal venoms have long been recognized as potentially rich source of biologically active molecules with the potential to be mined for the discovery of drugs, drug leads and/or biosimilars. In this work we demonstrate as a proof of concept a novel approach to explore venoms for potential biosimilarity to other drugs based on their ability to alter the transcriptomes of test cell lines followed by informatic searches and Connectivity Mapping to match the action of the venom on the cell gene expression to that of other drugs in the Connectivity Map (C-Map) database. As our test animal venom we chose Heloderma suspectum venom (Gila monster) since exendin-4, a glucagon-like peptide 1 receptor agonist, isolated from the venom is currently on the market to treat type 2 diabetes.

Proteomic anatomy of human skin.

Unlabelled: The extracellular matrix is composed of a variety of proteins which are essential for growth, wound healing, and fibrosis. It provides both structural support as well as contributing to the regulation of the local microenvironment. To further characterize the molecular composition of human skin we have undertaken a proteomic approach to identify proteins in three skin regions from two locations.

Endogenous concentrations of ouabain act as a cofactor to stimulate fluid secretion and cyst growth of in vitro ADPKD models via cAMP and EGFR-Src-MEK pathways.

In autosomal-dominant polycystic kidney disease (ADPKD), renal cysts develop by aberrant epithelial cell proliferation and transepithelial fluid secretion. We previously showed that ouabain increases proliferation of cultured human ADPKD cells via stimulation of the EGF receptor (EGFR)-Src-MEK/ERK signaling pathway. We examined whether ouabain affects fluid secretion and in vitro cyst growth of human ADPKD cell monolayers, ADPKD cell microcysts cultured in a three-dimensional collagen matrix, and metanephric organ cultures from Pkd1(m1Bei) mice.