Tenascin-C protein is induced by transforming growth factor-beta1 but does not correlate with time to tumor progression in high-grade gliomas.
BACKGROUND
Tenascin-C is an extracellular matrix protein known to correlate with prognosis in patients with glioblastoma, probably by stimulation of invasion and neoangiogenesis. Transforming Growth Factor-beta1 (TGF-beta1) plays an important role in the biology of high-grade gliomas, partly by regulating invasion of these tumors into parenchyma. This study was designed to evaluate if TGF-beta1 induces the expression and deposition of Tenascin-C in the extracellular matrix of high-grade gliomas which may be pivotal for the invasion of these tumors into healthy parenchyma.


METHODS
A series of 20 high-grade gliomas was stained immunohistochemically with Tenascin-C- and TGF-beta1- specific antibodies. Expression levels of both proteins were evaluated and correlated with each other, time to progression and molecular and morphological markers of invasion. A quantitative PCR assay was performed evaluating the induction of Tenascin-C mRNA by treatment with TGF-beta1 in vitro.


RESULTS
Tenascin-C was expressed in 18 of 19 (95%) evaluable tumors, whereas 14 of 20 tumors (70%) expressed TGF-beta1 in a significant percentage of cells. Treatment with TGF-beta1 did induce the expression of Tenascin-C at the mRNA and protein level in vitro. The expression of Tenascin-C and TGF-beta1 did neighter statistically correlate with each other nor with time to progression.


CONCLUSIONS
In our series, Tenascin-C and TGF-beta1 were expressed in the vast majority of high-grade gliomas. We could not detect a correlation of one of the proteins with time to progression. Nevertheless, we describe induction of Tenascin-C by TGF-beta1, possibly providing a mechanism for the invasion of high-grade gliomas into healthy parenchyma.
Hau
Peter
P
Department of Neurology, University of Regensburg, Universitätsstrasse 84, 93053, Regensburg, Germany. peter.hau@medbo.de
Kunz-Schughart
Leoni A
LA
Rümmele
Petra
P
Arslan
Füsun
F
Dörfelt
Anett
A
Koch
Horst
H
Lohmeier
Annette
A
Hirschmann
Birgit
B
Müller
Adolf
A
Bogdahn
Ulrich
U
Bosserhoff
Anja-Katrin
AK
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018316:Gliosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D019063:Tenascin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1