title: Involvement of large tenascin-C splice variants in breast cancer progression.
abstract: Alternative splicing of fibronectin-like type III (FNIII) repeats of tenascin-C (Tn-C) generates a number of splice variants. The distribution of large variants, typical components of provisional extracellular matrices that are up-regulated during tumor stroma remodeling, was here studied by immunoblotting and immunohistochemistry using a monoclonal antibody against the FNIII B domain (named 4C8MS) in a series of human breast cancers. Large Tn-C variants were found at only low levels in normal breast tissues, but were highly expressed at invading sites of intraductal cancers and in the stroma of invasive ductal cancers, especially at invasion fronts. There was a positive correlation between the expression of large Tn-C variants and the cell proliferation rate determined by immunolabeling of the Ki-67 antigen. Of the Tn-C recombinant fragments (all FNIII repeats or mFNIII FL, the conserved FNIII domain only, the epidermal growth factor-like domain, and the fibrinogen-like domain) which were expressed by CHO-K1 cells transfected with mouse Tn-C cDNAs, only the mFNIII FL enhanced in vitro migration and mitotic activity of mammary cancer cells derived from a Tn-C-null mouse. Addition of 4C8MS blocked the function of mFNIII FL. These findings provide strong evidence that the FNIII alternatively spliced region has important roles in tumor progression of breast cancer.
authors.affiliation: Department of Pathology, Mie University School of Medicine, Mie, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inada
authors.forename: Ilunga
authors.initials: I
authors.lastname: Kalembeyi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imanaka-Yoshida
authors.forename: Mirei
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Ray
authors.initials: R
authors.lastname: Okada
authors.forename: Koji
authors.initials: K
authors.lastname: Katsuta
authors.forename: Teruyo
authors.initials: T
authors.lastname: Sakakura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Majima
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics / Q000276:immunology; D019063:Tenascin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D005353:Fibronectins; D020033:Protein Isoforms; D019063:Tenascin