Mesenchymal cells contribute to the synthesis and deposition of the laminin-5 gamma2 chain in the invasive front of oral squamous cell carcinoma.
Tumour progression in oral squamous cell carcinoma (OSCC) is associated with a reorganisation of extracellular matrix. Laminin-5 (Ln-5) plays an important role for tumour migration and shows an increased expression in areas of direct tumour/stroma interactions. We have previously shown stromal spot like Ln-5/gamma2 chain deposits distant from the basement membrane region. In this study we have analysed which cell type is responsible for Ln-5/gamma2 chain synthesis in situ. Furthermore, we studied its spatial relation to TGF-beta1 as well as the Ln-5 modulating enzymes matrix metalloproteinase (MMP) 2, membrane type-1 (MT1-) MMP and bone morphogenetic protein (BMP-) 1 by different techniques including triple immunofluorescence labelling and in situ hybridisation in OSCC. We found that the stromal spot-like Ln-5 deposits occurred in the invasive front in the vicinity of mesenchymal cells and vessel structures. In particular, not only carcinoma cells but also mesenchymal cells were shown to express the Ln-5/gamma2 chain mRNA. Moreover, stromal Ln-5 deposits showed a spatial association with TGF-beta1 as well as with MT1-MMP and BMP-1. Based on these findings we suggest that mesenchymal cells contribute to the promotion of tumour cell migration as well as vessel formation in OSCC by providing and organising promigratory Ln-5 fragments.
Franz
Marcus
M
Institute of Pathology, Friedrich Schiller University, Ziegelmühlenweg 1, 07740 Jena, Germany.
Richter
Petra
P
Geyer
Christiane
C
Hansen
Torsten
T
Acuña
Lorena Dominguez
LD
Hyckel
Peter
P
Böhmer
Frank D
FD
Kosmehl
Hartwig
H
Berndt
Alexander
A
D000818:Animals; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; C400567:LAMC2 protein, human; D007797:Laminin; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D008666:Metalloendopeptidases; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14