Differential expression of tenascin-C splicing domains in urothelial carcinomas of the urinary bladder.
OBJECTIVE
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-C(L)) 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-C(L) 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.


CONCLUSIONS
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.
Berndt
Alexander
A
Institute of Pathology, Friedrich Schiller University, Ziegelmühlenweg 1, 07740, Jena, Germany. Alexander.Berndt@med.uni-jena.de
Anger
Katharina
K
Richter
Petra
P
Borsi
Laura
L
Brack
Simon
S
Silacci
Michela
M
Franz
Marcus
M
Wunderlich
Heiko
H
Gajda
Mieczyslaw
M
Zardi
Luciano
L
Neri
Dario
D
Kosmehl
Hartwig
H
D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000737:chemistry; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019154:Protein Splicing; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000032:analysis* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology; D019459:Urothelium / Q000737:chemistry
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019063:Tenascin