title: Clinical impact and functional aspects of tenascin-C expression during glioma progression.
abstract: The extracellular matrix protein tenascin-C is expressed in processes like embryogenesis and wound healing and in neoplasia. Tenascin-C expression in gliomas has been described previously; however, the relation to clinical data remains inconsistent. Generally, analysis of tenascin-C function is difficult due to different alternatively spliced isoforms. Our studies focus on changes in tenascin-C expression in human gliomas, correlating these changes with tumor progression and elucidating the functional role of the glioma cell-specific tenascin-C isoform pool. Eighty-six glioma tissues of different World Health Organization (WHO) grades were analyzed immunohistochemically for tenascin-C expression. The influence of the specific tenascin-C isoforms produced by glioblastoma cells on proliferation and migration was examined in vitro using blocking antibodies recognizing all isoforms. In general, tenascin-C expression increased with tumor malignancy. Perivascular staining of tenascin-C around tumor-supplying blood vessels was observed in all glioblastoma tissues, whereas in WHO II and III gliomas, perivascular tenascin-C staining appeared less frequently. The appearance of perivascular tenascin-C correlated significantly with a shorter disease-free time. Analysis of proliferation and migration in the presence of blocking antibodies revealed an inhibition of proliferation by around 30% in all 3 glioblastoma cell cultures, as well as a decrease in migration of 30.6-46.7%. Thus we conclude that the endogenous pool of tenascin-C isoforms in gliomas supports both tumor cell proliferation and tumor cell migration. In addition, our data on the perivascular staining of tenascin-C in WHO II and III gliomas and its correlation with a shorter disease-free time suggest that tenascin-C may be a new and potent prognostic marker for an earlier tumor recurrence.
authors.affiliation: Molecular Biology Laboratory, Neurosurgery Hospital, University of Heidelberg, Germany. Christel_Herold-Mende@med.uni-heidelberg.de
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Margareta M
authors.initials: MM
authors.lastname: Mueller
authors.forename: Mario M
authors.initials: MM
authors.lastname: Bonsanto
authors.forename: Horst Peter
authors.initials: HP
authors.lastname: Schmitt
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunze
authors.forename: Hans-Herbert
authors.initials: HH
authors.lastname: Steiner
mesh_terms: D000911:Antibodies, Monoclonal; D001932:Brain Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D018450:Disease Progression; D005909:Glioblastoma / Q000378:metabolism* / Q000503:physiopathology; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009367:Neoplasm Staging; D019063:Tenascin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D019063:Tenascin