title: L1 augments cell migration and tumor growth but not beta3 integrin expression in ovarian carcinomas.
abstract: L1 is a neural cell adhesion molecule involved in cell migration, axon growth and guidance. Recent data have shown that L1 is overexpressed in ovarian and endometrial tumors and is associated with bad prognosis. How L1 promotes tumor progression is presently unknown. Here we show that L1 expression is predominantly confined to the invasive front of ovarian carcinomas. Overexpression of L1 in carcinoma cell lines by adenovirus-mediated gene transfer enhanced the haptotactic cell migration on extracellular matrix proteins. Expression of L1 augmented tumor growth of carcinomas xenografted in nonobese diabetic/severe combined immunodeficient mice (NOD/SCID). A recent report has demonstrated L1-dependent upregulation of beta3 integrin involving activation of the extracellular signal-regulated kinase (erk) pathway. We find that L1 and beta3 integrin are not coexpressed in ovarian carcinoma tissues. Overexpression of L1 did not upregulate beta3 integrin in ovarian carcinoma cell lines but could do so in HEK293 cells. Our results suggest that L1 could drive progression by enhancing cell migration and tumor growth but that L1 dependent and erk-regulated gene expression requires cell-type specific elements.
authors.affiliation: Tumor Immunology Programme, D010, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gast
authors.forename: Svenja
authors.initials: S
authors.lastname: Riedle
authors.forename: Svenja
authors.initials: S
authors.lastname: Riedle
authors.forename: Heidi
authors.initials: H
authors.lastname: Schabath
authors.forename: Sabine
authors.initials: S
authors.lastname: Schlich
authors.forename: Annette
authors.initials: A
authors.lastname: Schneider
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Issa
authors.forename: Alexander
authors.initials: A
authors.lastname: Stoeck
authors.forename: Mina
authors.initials: M
authors.lastname: Fogel
authors.forename: Safwan
authors.initials: S
authors.lastname: Joumaa
authors.forename: Till
authors.initials: T
authors.lastname: Wenger
authors.forename: Ingrid
authors.initials: I
authors.lastname: Herr
authors.forename: Paul
authors.initials: P
authors.lastname: Gutwein
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D007668:Kidney; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D039661:Integrin beta3; D039842:Neural Cell Adhesion Molecule L1; D034741:RNA, Small Interfering