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.
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.
Franz
Marcus
M
Institute of Pathology, Friedrich Schiller University, Ziegelmühlenweg 1, 07740, Jena, Germany.
Hansen
Torsten
T
Richter
Petra
P
Borsi
Laura
L
Böhmer
Frank-D
FD
Hyckel
Peter
P
Schleier
Peter
P
Katenkamp
Detlef
D
Zardi
Luciano
L
Kosmehl
Hartwig
H
Berndt
Alexander
A
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*
C400567:LAMC2 protein, human; D007797:Laminin; D019063:Tenascin