Expression, intracellular localization and maturation of cysteine cathepsins in renal embryonic and cancer cell lines

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Abstract

Cysteine cathepsins play an important role in tumor development and metastasis. The expression of these enzymes is often increased in many types of tumor cells. Cysteine cathepsins contribute to carcinogenesis through a number of mechanisms, including proteolysis of extracellular matrix and signaling molecules on the cell surface, as well as degradation of transcription factors and disruption of signaling cascades in the cell nucleus. Distinct oncogenic functions have been reported for several members of the cysteine cathepsin family in various types of cancer, but a comparative study of all eleven cysteine cathepsins in one experimental model is still missing. In this work, we assessed and compared the expression, localization, and maturation of all eleven cysteine cathepsins in embryonic kidney cells HEK293 and kidney cancer cell lines 769-P and A-498. We found that the expression of cathepsins V, B, Z, L, and S was 3- to 9-fold higher in kidney tumor cells than in embryonic cells. We also showed that all cysteine cathepsins were present in varying amounts in the nucleus of both embryonic and tumor cells. Notably, more than half of the cathepsin Z or K and over 88% of cathepsin F were localized in tumor cell nuclei. Moreover, mature forms of cysteine cathepsins were more prevalent in tumor cells than in embryonic cells. These results can be further used to develop novel diagnostic tools and may assist in the investigation of cysteine cathepsins as potential therapeutic targets.

About the authors

A. S Frolova

Institute of Molecular Medicine, Sechenov First Moscow State Medical University;Scientific Center for Translation Medicine, Sirius University of Science and Technology

119991 Moscow, Russia;354340 Sochi, Russia

N. K Tikhomirova

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

119992 Moscow, Russia

I. I Kireev

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

119992 Moscow, Russia

E. Yu Zernii

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

119992 Moscow, Russia

A. Parodi

Scientific Center for Translation Medicine, Sirius University of Science and Technology

354340 Sochi, Russia

K. I Ivanov

Scientific Center for Translation Medicine, Sirius University of Science and Technology

354340 Sochi, Russia

A. A Zamyatnin

Institute of Molecular Medicine, Sechenov First Moscow State Medical University;Scientific Center for Translation Medicine, Sirius University of Science and Technology;Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University;Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University

Email: zamyat@belozersky.msu.ru
119991 Moscow, Russia;354340 Sochi, Russia;119992 Moscow, Russia;119234 Moscow, Russia

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