Distribution of laminin and fibronectin isoforms in oral mucosa and oral squamous cell carcinoma

Abstract

SummaryThe expression of laminin and fibronectin isoforms varies with cellular maturation and differentiation and these differences may well influence cellular processes such as adhesion and motility. The basement membrane (BM) of fetal oral squamous epithelium contains the laminin chains, α2, α3, α5, β1, β2, β3, γ1 and γ2. The BM of adult normal oral squamous epithelium comprises the laminin chains, α3, α5, β1, β3, γ1 and γ2. A re-expression of the laminin α2 and β2 chains could be shown in adult hyperproliferative, dysplastic and carcinomatous lesions.In dysplasia and oral squamous cell carcinoma (OSCC), multifocal breaks of the BM are present as indicated by laminin chain antibodies. These breaks correlate to malignancy grade in their extent. Moreover, in the invasion front the α3 and γ2 chain of laminin-5 can immunohistochemically be found outside the BM within the cytoplasm of budding carcinoma cells and in the adjacent stroma. The correlation between the morphological pattern of invasive tumour clusters and a laminin-5 immunostaining in the adjacent stroma may suggest, first, that a laminin-5 deposition outside the BM is an immunohistochemical marker for invasion and second, that OSCC invasion is guided by the laminin-5 matrix. Expression of oncofetal fibronectins (IIICS de novo glycosylated fibronectin and ED-B fibronectin) could be demonstrated throughout the stromal compartment. However, the ED-B fibronectin synthesizing cells (RNA/RNA in situ hybridization) are confined to small stroma areas and to single stroma and inflammatory cells in the invasion front. A correlation of the number of ED-B fibronectin synthesizing cells to malignancy grade could not be seen. ED-B fibronectin mRNA-positive cells seem to be concentrated in areas of fibrous stroma recruitment with a linear alignment of stromal fibro-/myofibroblasts (desmoplasia). Double staining experiments (ED-B fibronectin in situ hybridization and α-smooth muscle actin immunohistochemistry) indicated that the stroma myofibroblasts are a preferential source of ED-B fibronectin. In conclusion, in OSCC, a fetal extracellular matrix conversion is demonstrable. Tumour cells (laminin α2 and β2 chain) and recruited stromal myofibroblasts (oncofetal ED-B fibronectin) contribute to the fetal extracellular matrix milieu.

Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

“…This is supported by other studies in different tumour types (Zardi et al, 1987;Carnemolla et al, 1989;Castellani et al, 1994;Kaczmarek et al, 1994;Neri et al, 1997;D'Ovidio et al, 1998;Kosmehl et al, 1999;Tarli et al, 1999;Viti et al, 1999;Ebbinghaus et al, 2004).…”

“…However, it is overexpressed during active tissue remodelling, for example, angiogenesis in tumours, wound healing and embryogenesis Kaspar et al, 2006). It has been shown to accumulate specifically around neovasculature in studies of many different tumour types, making it a good marker for angiogenesis (Carnemolla et al, 1989;Kaczmarek et al, 1994;Neri et al, 1997;Kosmehl et al, 1999;Tarli et al, 1999;Viti et al, 1999;Demartis et al, 2001;Castellani et al, 2002;Birchler et al, 2003;Ebbinghaus et al, 2004).…”

Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

“…A more recent study demonstrated that oncofetal fibronectins are present throughout the stromal compartment associated with SCC. Further examination revealed that stromal fibro/myofibroblasts were the preferential source of this fibronectin (Kosmel et al, 1999). Thus, in this study it was concluded that in SCC, conversion to a fetal ECM is occurring.…”

Effects of human fibroblasts from myelometaplasic and non-myelometaplasic hematopoietic tissues on CD34+ stem cells

“…11 Thus, all fibroblasts isolated from MM spleen, unlike BM-derived fibroblasts, expressed ␣-sm-actin, ED-B fibronectin and tenascin, which is characteristic of myofibroblasts, found only in pathologic stroma. 17,18 Furthermore, MM spleen-derived fibroblasts also showed higher expression levels of specific surface adhesion molecules for blood cell interactions, i.e., ICAM-1, VLA-4 and CD4 as well as hematopoietic cytokines, i.e., GM-CSF and IL-11.…”