title: ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells.
abstract: ADAMs are transmembrane multifunctional proteins that contain disintegrin and metalloprotease domains. ADAMs act in a diverse set of biological processes, including fertilization, inflammatory responses, myogenesis, cell migration, cell proliferation and ectodomain cleavage of membrane proteins. These proteins also have additional functions in pathological processes as cancer and metastasis development. ADAM9 is a member of ADAM protein family that is overexpressed in several types of human carcinomas. The aim of this study was to investigate the role of ADAM9 in hematogenous and lymphatic tumor cell dissemination assisting the development of new therapeutic tools. The role of ADAM9 in the interaction of breast tumor cells (MDA-MB-231) and endothelial cells was studied through RNA silencing. ADAM9 silencing in MDA-MB-231 cells had no influence in expression of several genes related to the metastatic process such as ADAM10, ADAM12, ADAM17, cMYC, MMP9, VEGF-A, VEGF-C, osteopontin and collagen XVII. However, there was a minor decrease in ADAM15 expression but an increase in that of MMP2. Moreover, ADAM9 silencing had no effect in the adhesion of MDA-MB-231 cells to vascular (HMEC-1 and HUVEC) and lymphatic cells (HMVEC-dLyNeo) under flow condition. Nevertheless, siADAM9 in MDA-MB-231 decreased transendothelial cell migration in vitro through HUVEC, HMEC-1 and HMVEC-dLyNeo (50%, 40% and 32% respectively). These results suggest a role for ADAM9 on the extravasation step of the metastatic cascade through both blood and lymph vessels.
authors.affiliation: Departamento de Ciências Fisiológicas, Rodovia Washington Luís, Km 235, CEP 13565-905, São Carlos, SP, Brazil. Electronic address: kelli_micocci@hotmail.com.
authors.forename: Kelli Cristina
authors.initials: KC
authors.lastname: Micocci
authors.affiliation: Departamento de Ciências Fisiológicas, Rodovia Washington Luís, Km 235, CEP 13565-905, São Carlos, SP, Brazil.
authors.forename: Milene Nóbrega de Oliveira
authors.initials: MN
authors.lastname: Moritz
authors.affiliation: Departamento de Ciências Fisiológicas, Rodovia Washington Luís, Km 235, CEP 13565-905, São Carlos, SP, Brazil.
authors.forename: Rafael Luis Bressani
authors.initials: RL
authors.lastname: Lino
authors.affiliation: Departamento de Biologia Celular, Rua São Francisco Xavier, 524, Pavilhão Haroldo Lisboa da Cunha - 2nd Floor, Rio de Janeiro, RJ, Brazil.
authors.forename: Laila Ribeiro
authors.initials: LR
authors.lastname: Fernandes
authors.affiliation: Departamento de Biologia Celular, Rua São Francisco Xavier, 524, Pavilhão Haroldo Lisboa da Cunha - 2nd Floor, Rio de Janeiro, RJ, Brazil.
authors.forename: Antonio Gilclêr Ferreira
authors.initials: AG
authors.lastname: Lima
authors.affiliation: Departamento de Biologia Celular, Rua São Francisco Xavier, 524, Pavilhão Haroldo Lisboa da Cunha - 2nd Floor, Rio de Janeiro, RJ, Brazil.
authors.forename: Camila Castro
authors.initials: CC
authors.lastname: Figueiredo
authors.affiliation: Departamento de Biologia Celular, Rua São Francisco Xavier, 524, Pavilhão Haroldo Lisboa da Cunha - 2nd Floor, Rio de Janeiro, RJ, Brazil.
authors.forename: Verônica
authors.initials: V
authors.lastname: Morandi
authors.affiliation: Departamento de Ciências Fisiológicas, Rodovia Washington Luís, Km 235, CEP 13565-905, São Carlos, SP, Brazil.
authors.forename: Heloisa Sobreiro
authors.initials: HS
authors.lastname: Selistre-de-Araujo
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018715:Microscopy, Video; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; C098660:ADAM15 protein, human; C098339:ADAM9 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: ADAM9; Blood and lymphatic endothelial cells; Breast cancer