Synthesis and protein distribution of the unspliced large tenascin-C isoform in oral squamous cell carcinoma

The inclusion dr Omission of the alternatively spliced region in the tenasc in-C (Tn-C) mRNA gives rise to the large (Tn-C-L) or small (Tn-C-s) variant , respectively. Tn-C-L is thought to be a typical component of provisional extracellular matrices (ECMs) and is expressed during tumour stroma remodel ling. Tn-C-L synthesis has been studied using RNA/RNA in situ hybridization , and Tn-C-L protein distribution, using immunohistochemistry (clone BC-2), in 18 oral squamous cell carcinomas (OSCCs) of different grades of maligna ncy. While the Tn-C-L protein was demonstrated within the whole stromal com partment regardless of grade of malignancy, the majority of the Tn-C-L mRNA signal-bearing cells were carcinoma cells. Only a few stromal myofibroblas ts were able to synthesize Tn-C-L, as revealed by alpha-smooth muscle actin double staining. In web-differentiated carcinomas (G1), the Tn-C-L synthes izing carcinoma cells were localized as a single positive cell layer in the tumour stroma interface, particularly in invasive areas. A higher grade of malignancy (G2/G3) is associated with a significantly increased number of Tn-C-L synthesizing carcinoma cells randomly distributed within the invadin g tumour areas. Double-staining experiments (Tn-C-L mRNA ISH/BC-2 immunohis tochemistry) indicate that these cells are capable of organizing and deposi ting a three-dimensional Tn-C-L matrix. Even though an instructive and/or i nductive role of the carcinoma cells in tumour stroma formation cannot be e xcluded, these results demonstrate that carcinoma cells can directly produc e the ECM components of tumour stroma, Copyright (C) 1999 John Whey & Sons, Ltd.