Tenascin isoforms: possible targets for diagnosis and therapy of cancer and mechanisms regulating their expression

Abstract

Functionally different tenascin (TN) isoforms containing varying numbers of III homology repeats are generated by alternative splicing of a single TN primary transcript. It has recently been reported that the larger TN isoform is, in general, more expressed in neoplastic tissues than in the normal tissues from which the tumor originates. This is due, at least in breast lesions, to the high proliferative activity of stromal elements. In fact, TN splicing is cell-cycle dependent, thus offering a viable system to study the molecular mechanisms that regulate alternative splicing and suggesting that cell-cycle dependent modifications in the splicing pattern of primary transcripts (which very likely are not limited to the TN pre-mRNA) may also be a cell-cycle regulatory mechanism. Furthermore, the very high accumulation of the larger TN isoform in neoplasia allows wider diagnostic and therapeutic monoclonal antibodies specific for the larger TN isoforms be considered for a number of tumors.