TY  - JOUR
A1  - Clees, Ada-Sophia
A1  - Stolp, Verena
A1  - Häupl, Björn
A1  - Fuhrmann, Dominik Christian
A1  - Wempe, Frank
A1  - Seibert, Marcel
A1  - Weber, Sarah
A1  - Banning, Antje
A1  - Tikkanen, Ritva
A1  - Williams, Richard
A1  - Brüne, Bernhard
A1  - Serve, Hubert
A1  - Schnütgen, Frank
A1  - Metzler, Ivana von
A1  - Kurrle, Nina Susanne
T1  - Identification of the cysteine protease legumain as a potential chronic hypoxia-specific multiple myeloma target gene
T2  - Cells
N2  - 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.
KW  - asparaginyl endopepdidase (AEP)
KW  - chronic hypoxia
KW  - glycolysis
KW  - legumain
KW  - multiple myeloma
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/81850
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-818505
SN  - 2073-4409
N1  - 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).
VL  - 11
IS  - 2, art. 292
SP  - 1
EP  - 26
PB  - MDPI
CY  - Basel
ER  -