Differential expression of tenascin-C splicing domains in urothelial carcinomas of the urinary bladder

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Abstract

Purpose

Through alternative splicing of the extracellular matrix protein tenascin-C (Tn-C) primary transcript nine type III homology repeats can be independently included or omitted. Large, low spliced Tn-C variants (Tn-CL) are preferentially expressed during tissue remodelling processes like tumour invasion to modulate cell migration. The study was aimed to evaluate the differential expression of Tn-C splicing domains in urinary bladder carcinoma with respect to the invasive behaviour.

Methods

The deposition and synthesis of the Tn-C splicing domains A1-D was analysed in 34 urinary bladder carcinomas by semiquantitative immunohistochemistry using domain specific antibodies and by RT-PCR. Results were correlated to tumour stage and grade.

Results

There is a significant increase of Tn-CL with higher tumour stage and grade. Immunohistochemistry revealed a more restricted distribution pattern of A1, B, and/or D domain containing Tn-C variants to invasive tumours, tumour vessels, and to destructed muscle. The mRNA expression patterns of the domains A1-A3 are similar among the different carcinomas. Stronger differences exist in the region from the B to D domain. In general, the domains AD1/C are rarely expressed. AD1 domain expression seems to be connected with compact invasion pattern.

Conclusion

In urinary bladder carcinoma a differential expression of Tn-C splicing variants exists in dependence of tumour type, vascularization, and invasive behaviour. Therefore, the detection of different Tn-C splicing domains could be useful for assessment of muscle invasion, tumour surveillance, as well as target structures for antibody based tumour detection and therapy.

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