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

摘要

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.