Identification of the cysteine protease legumain as a potential chronic hypoxia-specific multiple myeloma target gene

  • Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1–6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the mRNA expression of previously determined hypoxia markers to define the temporal adaptation of MM cells to chronic hypoxia. Subsequent analyses of the global proteome in MM cells and the stromal cell line HS-5 revealed hypoxia-dependent regulation of proteins, which directly or indirectly upregulate glycolysis. In addition, chronic hypoxia led to MM-specific regulation of nine distinct proteins. One of these proteins is the cysteine protease legumain (LGMN), the depletion of which led to a significant growth disadvantage of MM cell lines that is enhanced under hypoxia. Thus, herein, we report a methodologic strategy to examine MM cells under physiologic hypoxic conditions in vitro and to decipher and study previously masked hypoxia-specific therapeutic targets such as the cysteine protease LGMN.
Metadaten
Author:Ada-Sophia CleesGND, Verena Stolp, Björn Häupl, Dominik Christian FuhrmannORCiDGND, Frank WempeGND, Marcel SeibertGND, Sarah WeberORCiD, Antje BanningGND, Ritva TikkanenORCiDGND, Richard Williams, Bernhard BrüneORCiD, Hubert ServeORCiDGND, Frank SchnütgenORCiDGND, Ivana von Metzler, Nina Susanne KurrleORCiDGND
URN:urn:nbn:de:hebis:30:3-818505
DOI:https://doi.org/10.3390/cells11020292
ISSN:2073-4409
Parent Title (English):Cells
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2022/01/15
Date of first Publication:2022/01/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/01/29
Tag:asparaginyl endopepdidase (AEP); chronic hypoxia; glycolysis; legumain; multiple myeloma
Volume:11
Issue:2, art. 292
Article Number:292
Page Number:1
First Page:1
Last Page:26
Note:
The project is part of the LOEWE Main Research Focus DynaMem, which is funded by the German Federal State of Hesse within the framework of the Hessian initiative for scientific and economic excellence (LOEWE).
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International