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

The inclusion or omission of the alternatively spliced region in the tenascin‐C (Tn‐C) mRNA gives rise to the large (Tn‐CL) or small (Tn‐CS) variant, respectively. Tn‐CL is thought to be a typical component of provisional extracellular matrices (ECMs) and is expressed during tumour stroma remodelling. Tn‐CL synthesis has been studied using RNA/RNA in situ hybridization, and Tn‐CL protein distribution, using immunohistochemistry (clone BC‐2), in 18 oral squamous cell carcinomas (OSCCs) of different grades of malignancy. While the Tn‐CL protein was demonstrated within the whole stromal compartment regardless of grade of malignancy, the majority of the Tn‐CL mRNA signal‐bearing cells were carcinoma cells. Only a few stromal myofibroblasts were able to synthesize Tn‐CL, as revealed by α‐smooth muscle actin double staining. In well‐differentiated carcinomas (G1), the Tn‐CL synthesizing 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‐CL synthesizing carcinoma cells randomly distributed within the invading tumour areas. Double‐staining experiments (Tn‐CL mRNA ISH/BC‐2 immunohistochemistry) indicate that these cells are capable of organizing and depositing a three‐dimensional Tn‐CL matrix. Even though an instructive and/or inductive role of the carcinoma cells in tumour stroma formation cannot be excluded, these results demonstrate that carcinoma cells can directly produce the ECM components of tumour stroma. Copyright © 1999 John Wiley & Sons, Ltd.

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