Consistent with in situ findings, NGF increased by two-fold in the hepatic blood from metastasis-bearing mice. NGF also significantly increased in the supernatant of both HSC given tumor cell-conditioned medium(CM),and hepatocytes given tumor-activated HSC-CM, SBI-0206965 but not tumor cell-CM. Recombinant NGF dose-dependently increased chemotactic migration, but not proliferation and adhesion of neurotrophin receptor-expressing tumor cells in vitro.
HSC migration-stimulating activity of VEGF and tumor-activated hepatocytes was also NGF-mediated as shown with anti-NGF antibodies. Our results demonstrate that hepatocyte- and HSC-derived myofibroblasts secrete NGF in the hepatic metastasis microenvironment of colorectal carcinoma and suggest that NGF contributes to hepatic metastasis development through the specific activation of tumor and stromal cell migration. Poster No. 124 Transcript Profiling for Epithelial – Mesenchymal Transition (EMT) Search for EMT Signature and Validation on Clinical
Samples An De Bondt2, Thierry Grand-Perret 1 , Janine Arts1, Tamara Geerts1, Lutgart Janssen1, An Boeckx1, Nele Vloemans1, Ilse Van den this website Wyngaert2, Willem Talloen3, Hinrich Göhlmann2, Pieter J. Peeters2 1 Oncology Discovery, Ortho Biotech Research & Development, a division of Janssen Pharmaceutica NV, Beerse, Antwerpen, Belgium, 2 Functional Genomics and Molecular Profiling, Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Antwerpen, Belgium, 3 Nonclinical Biostatistics, Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutica NV, Beerse,
Antwerpen, Belgium Background: Patient stratification becomes Sitaxentan increasingly important for metastatic cancer treatment. Initiation of metastasis involves invasion and increased cell motility, which has many similarities to Epithelial-Mesenchymal-Transition (EMT), including a loss of cell-cell adhesion mediated by E-cadherin down-regulation. Aim: The aim of this study is to identify a set of genes that could be a biomarker for metastatic risk to be used on tumor biopsies. More specifically, a gene expression signature discriminating epithelial from mesenchymal cell phenotypes. Methods: First we have focused on known genes related to EMT based on literature. Second, we investigated whether we could identify another unbiased set of genes, solely based on expression data of cell lines, which can discriminate epithelial from mesenchymal cells. A refined principle component selleck screening library analysis, based on this subset of genes, identifies the weight of each gene in this signature. Taking these weights together with their expression levels make up a so-called composite gene expression measure. This has been applied to data from clinical samples.