mRNA expression and protein distribution of the unspliced tenascin-C isoform in prostatic adenocarcinoma

The inclusion or omission of the alternatively spliced region in the tenascin-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 remodelling in cancer. Tn-C(L) mRNA expression and protein distribution have been studied in 44 prostatic adenocarcinomas using RNA/RNA in situ hybridization supplemented by reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemistry (clone BC-2). While the Tn-C(L) protein was demonstrated within tumour stroma, Tn-C(L) mRNA expression was mainly observed in carcinoma cells, regardless of the histological grade of the tumour. Carcinoma cells containing Tn-C(L) mRNA were particularly localized at the tumour invasion front. Tn-C(L) mRNA was also identified in benign prostatic hyperplasia, where it was present exclusively in the basal cell layer, and in prostatic intraepithelial neoplasia in which there was partial loss of positive basal cells and increasing positivity of luminal cells. Furthermore, newly formed tumour blood vessels and inflammatory and stromal cells take part in the expression of Tn-C(L) and are involved in the formation of a provisional tumour matrix. It is concluded that deposits of Tn-C(L) indicate rebuilding processes in non-neoplastic as well as in neoplastic prostatic tissues. In respect of the Tn-C(L) synthesis in budding prostatic carcinoma cells, the results demonstrate that tumour cells can directly produce the ECM components of carcinoma stroma, creating conditions that facilitate the process of invasion.