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Tenascin isoforms: possible targets for diagnosis and therapy of cancer and mechanisms regulating their expression
1Laboratory of Cell Biology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
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.
Insights
The larger tenascin (TN) isoform is more abundant in tumors due to cell-cycle dependent splicing. This finding suggests TN splicing may regulate cell cycles and offers new diagnostic and therapeutic targets for cancer.
Area of Science:
- Molecular biology
- Cancer research
- Cell biology
Background:
- Tenascin (TN) isoforms are generated by alternative splicing of a single TN primary transcript.
- Larger TN isoforms are generally more expressed in neoplastic tissues than in normal tissues.
- This increased expression, particularly in breast lesions, is linked to the high proliferative activity of stromal elements.
Purpose of the Study:
- To investigate the cell-cycle dependence of TN splicing.
- To explore the role of cell-cycle dependent splicing modifications as a regulatory mechanism.
- To assess the potential of larger TN isoforms as diagnostic and therapeutic targets in neoplasia.
Main Methods:
- Analysis of alternative splicing patterns of tenascin (TN) transcripts.
- Correlation of TN isoform expression with cell-cycle status in various tissues.
- Evaluation of TN splicing as a cell-cycle regulatory mechanism.
Main Results:
- Tenascin (TN) splicing is demonstrated to be cell-cycle dependent.
- Cell-cycle dependent modifications in splicing patterns of primary transcripts may represent a regulatory mechanism.
- High accumulation of larger TN isoforms in neoplasia is confirmed.
Conclusions:
- Cell-cycle dependent splicing of tenascin (TN) is a key factor in its differential expression in tumors.
- This mechanism offers insights into broader cell-cycle regulatory processes involving alternative splicing.
- Larger TN isoforms present viable targets for developing diagnostic and therapeutic monoclonal antibodies for various tumors.