Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter June 11, 2010

Nuclear cysteine cathepsin variants in thyroid carcinoma cells

Sofia Tedelind, Kseniia Poliakova, Amanda Valeta, Ruth Hunegnaw, Eyoel Lemma Yemanaberhan, Nils-Erik Heldin, Junichi Kurebayashi, Ekkehard Weber, Nataša Kopitar-Jerala, Boris Turk, Matthew Bogyo and Klaudia Brix
From the journal

Abstract

The cysteine peptidase cathepsin B is important in thyroid physiology by being involved in thyroid prohormone processing initiated in the follicular lumen and completed in endo-lysosomal compartments. However, cathepsin B has also been localized to the extrafollicular space and is therefore suggested to promote invasiveness and metastasis in thyroid carcinomas through, e.g., ECM degradation. In this study, immunofluorescence and biochemical data from subcellular fractionation revealed that cathepsin B, in its single- and two-chain forms, is localized to endo-lysosomes in the papillary thyroid carcinoma cell line KTC-1 and in the anaplastic thyroid carcinoma cell lines HTh7 and HTh74. This distribution is not affected by thyroid stimulating hormone (TSH) incubation of HTh74, the only cell line that expresses a functional TSH-receptor. Immunofluorescence data disclosed an additional nuclear localization of cathepsin B immunoreactivity. This was supported by biochemical data showing a proteolytically active variant slightly smaller than the cathepsin B proform in nuclear fractions. We also demonstrate that immunoreactions specific for cathepsin V, but not cathepsin L, are localized to the nucleus in HTh74 in peri-nucleolar patterns. As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins.


Corresponding author

Received: 2010-2-8
Accepted: 2010-5-20
Published Online: 2010-06-11
Published in Print: 2010-08-01

©2010 by Walter de Gruyter Berlin New York

Scroll Up Arrow