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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Acknowledgements
The authors would like to thank Lab. Ing. Carola König, Susanne Köllner, and Christiane Geier for excellent technical assistance. The study was partially supported by the Thuringian Ministry of Science, Research and Art (ThMWFK) and IZKF of the University Jena (B307-04004), by the Associazione Italiana per la Ricerca sul Cancro (AIRC), and by the European Community. (FP6, LSH-CT-2003-5032, STROMA; this publication reflects only the authors view. The European Commission is not liable for any use that may be made of the information contained.) Moreover we are grateful to QIAGEN GmbH, Germany, for providing us with the β-actin primer sequences.
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Berndt, A., Anger, K., Richter, P. et al. Differential expression of tenascin-C splicing domains in urothelial carcinomas of the urinary bladder. J Cancer Res Clin Oncol 132, 537–546 (2006). https://doi.org/10.1007/s00432-006-0106-8
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DOI: https://doi.org/10.1007/s00432-006-0106-8