title: Influence of tumor-associated E-cadherin mutations on tumorigenicity and metastasis.
abstract: In this study, we investigated whether tumor-associated E-cadherin mutations impair the tumor-suppressive function of the cell adhesion molecule and influence metastasis formation in a severe combined immunodeficiency mouse model. The investigated E-cadherin mutations were in frame deletions of exons 8 (del 8) or 9 (del 9) and a point mutation in exon 8 (p8). Transfected human MDA-MB-435S carcinoma cells stably expressing wild-type (wt) or mutant E-cadherin were injected into the mouse mammary fat pad. Mice transplanted with wt E-cadherin transfectants developed significantly smaller tumors than animals transplanted with the E-cadherin-negative parental cell line. Animals transplanted with del 9 or p8 E-cadherin transfectants produced medium size tumors, indicating that these mutations impair the tumor-suppressive function of E-cadherin. In contrast, mice transplanted with del 8 E-cadherin transfectants developed tumors of approximately the same sizes as animals transplanted with wt E-cadherin expressing cells. Lung metastases were induced by all cell lines without significant differences. Immunohistochemical analysis of E-cadherin expression in the tumors revealed a heterogeneous staining pattern, indicating loss or down-regulation of E-cadherin in some tumor cells. Metastases were completely negative for E-cadherin. Our data suggest that the type of mutation determines whether the tumor-suppressive function of E-cadherin is impaired.
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Institut für Allgemeine Pathologie und Pathologische Anatomie, München, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Kremer
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Margit
authors.initials: M
authors.lastname: Fuchs
authors.forename: Armando
authors.initials: A
authors.lastname: Gamboa-Dominguez
authors.forename: Sieglinde
authors.initials: S
authors.lastname: Haye
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.forename: Erika
authors.initials: E
authors.lastname: Rosivatz
authors.forename: Christine
authors.initials: C
authors.lastname: Hermannstädter
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Birgit
authors.initials: B
authors.lastname: Luber
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005091:Exons; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014162:Transfection
chemical_list: D015820:Cadherins