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Endocrine Abstracts (2016) 41 EP1128 | DOI: 10.1530/endoabs.41.EP1128

1Jacobs University, Bremen, Germany; 2School of Pharmacy, Queen’s University, Belfast, UK; 3Department of Endocrinology and Metabolism, University Hospital, Essen, Germany.


Cysteine cathepsins are endo-lysosomal proteases that play crucial roles in thyroid physiology. However, in thyroid cancer, cathepsin B is overexpressed and secreted into the extracellular space, thus promoting migratory phenotypes of thyroid carcinoma cells through excessive extracellular matrix degradation. In addition, we have shown that N-terminally truncated forms of cathepsins B and V which lack the signal peptide and parts of the pro-peptide are localized to the nuclei of anaplastic thyroid carcinoma cells, while cathepsin L is present within endo-lysosomes as expected.

Cathepsins B, L, and V were also examined in a variety of different human thyroid carcinoma cell lines in comparison to normal thyroid epithelial cells by immunofluorescence and immunoblotting studies, revealing differential protein levels and/or subcellular distribution patterns of the different cathepsins in distinct cell lines. In particular, cathepsin V reached the nuclear compartment of thyroid carcinoma cells in vitro. For correlation of nuclear cysteine cathepsin activities to phenotypic characteristics of thyroid carcinoma cells, over-expression studies were performed with different molecular forms of the cysteine cathepsins B and V which were analysed as chimeric GFP-tagged proteins in synchronized cultures. Here, the results showed again that cathepsin V was trafficked to the nuclei of thyroid carcinoma cells.

In keeping with the hypothesis that nuclear tasks of cysteine cathepsins reside in the processing of nuclear proteins which are relevant for cell cycle progression, thyroid cancer tissue was analysed in addition. Cathepsin V was found prominently in the cellular nuclei of follicular thyroid carcinoma tissue, but not in papillary thyroid carcinoma.

We conclude that cathepsin V rather than cathepsins B and L might serve important functions within the nuclei of certain thyroid carcinoma cells.

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