title: Complex formation of the laminin-5 gamma2 chain and large unspliced tenascin-C in oral squamous cell carcinoma in vitro and in situ: implications for sequential modulation of extracellular matrix in the invasive tumor front.
abstract: Invasion and metastasis in oral squamous cell carcinoma (OSCC) are associated with changes in the extracellular matrix (ECM). We have previously shown an extracellular co-deposition of laminin-5 (Ln-5) and large unspliced tenascin-C (Tn-C(L)) in OSCC. Using a co-culture model of hTERT-BJ1 fibroblasts and the OSCC cell line PE/CA-PJ15, we demonstrate in the present study that Ln-5 and Tn-C(L) are not only co-deposited, but also form a physical complex which can be recovered by co-immunoprecipitation. In agreement with these results, examination of OSCC tissue specimens of different malignancy grade by means of confocal laser scanning microscopy revealed different patterns of Ln-5 and Tn-C(L) co-localization implicating complex formation also in vivo. A ribbon like co-localization was detected in subepithelial basement membranes around well differentiated OSCC parts and tumor clusters. Furthermore, a fibrillar Ln-5 gamma2 chain/Tn-C(L) co-localization occurred in the carcinoma stroma beneath tumor clusters. Additionally, at the site of ruptured basement membranes there were dot or strand like co-deposits of both molecules, but co-localizations were only rarely detectable. These different patterns may reflect a sequential modulation and reorganization of the ECM in the tumor/stroma interface as it occurs in different stages of OSCC invasion.
authors.affiliation: Institute of Pathology, Friedrich Schiller University, Ziegelmühlenweg 1, 07740, Jena, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Franz
authors.forename: Torsten
authors.initials: T
authors.lastname: Hansen
authors.forename: Petra
authors.initials: P
authors.lastname: Richter
authors.forename: Laura
authors.initials: L
authors.lastname: Borsi
authors.forename: Frank-D
authors.initials: FD
authors.lastname: Böhmer
authors.forename: Peter
authors.initials: P
authors.lastname: Hyckel
authors.forename: Peter
authors.initials: P
authors.lastname: Schleier
authors.forename: Detlef
authors.initials: D
authors.lastname: Katenkamp
authors.forename: Luciano
authors.initials: L
authors.lastname: Zardi
authors.forename: Hartwig
authors.initials: H
authors.lastname: Kosmehl
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
mesh_terms: D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007797:Laminin / Q000096:biosynthesis*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D019063:Tenascin / Q000096:biosynthesis*
chemical_list: C400567:LAMC2 protein, human; D007797:Laminin; D019063:Tenascin