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Scand J Gastroenterol. 2001 Nov;36(11):1204-10.

Evidence for the decreased expression of the latent TGF-beta binding protein and its splice form in human liver tumours.

Author information

  • 1Dept. of Clinical Chemistry and Central Laboratory, Philipps University, Marburg, Germany. sylke.roth-eichhorn@mailbox.tu-dresden.de

Abstract

BACKGROUND:

Recently, a splice form of the latent TGF-beta binding protein (LTBP-1) was identified in the liver lacking potential important sequences for matrix association and proteinase cleavage (LTBP-1D, -1delta53). For a better understanding of the unknown (patho)physiological role, the expression levels of LTBP-1D and LTBP-1 (full length) were investigated in normal and malignant human liver on the mRNA and protein level.

METHODS:

Normal liver (5 specimens), hepatocellular carcinoma (4 specimens) and fibrolamellar carcinoma (2 specimens) were examined by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry, for which specific antibodies were generated.

RESULTS:

The mRNA levels of LTBP-1/-1D in malignant liver tissues are decreased in comparison to normal liver--more so in HCC than in FLC. This finding was confirmed by a strong decrease of immunostaining of LTBP-1/-1D in neoplastic parenchymal cells of HCC and FLC. However, the intensity of LTBP-1 (full length) protein staining was increased in the extracellular matrix of the carcinomas, while LTBP-1D was not detectable in the matrix.

CONCLUSION:

Since TGF-beta is known to be over-expressed in liver tumours, the results suggest its enhanced synthesis without binding to LTBP-1. This probably influences the availability of bioactive TGF-beta in the tumour tissue. The missing matrix localization of LTBP-1D indicates that the hinge region containing a heparin-binding site is essential for the binding of LTBP-1 in the extracellular matrix. LTBP-1D may fulfil specific functions for the latency of matrix-unbound TGF-beta.

PMID:
11686222
[PubMed - indexed for MEDLINE]
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