Next Article in Journal
RNA Molecular Signature Profiling in PBMCs of Sporadic ALS Patients: HSP70 Overexpression Is Associated with Nuclear SOD1
Next Article in Special Issue
Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements
Previous Article in Journal
The Longevity-Associated Variant of BPIFB4 Reduces Senescence in Glioma Cells and in Patients’ Lymphocytes Favoring Chemotherapy Efficacy
Previous Article in Special Issue
DSTYK Enhances Chemoresistance in Triple-Negative Breast Cancer Cells
Article

Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene

1
Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe-University Frankfurt, 60590 Frankfurt, Germany
2
German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
3
Frankfurt Cancer Institute, Goethe-University Frankfurt, 60596 Frankfurt, Germany
4
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany
5
Institute of Biochemistry, Faculty of Medicine, University of Giessen, 35392 Giessen, Germany
6
Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work as the first authors.
These authors contributed equally to this work as supervising authors.
Academic Editor: Marco Cippitelli
Cells 2022, 11(2), 292; https://doi.org/10.3390/cells11020292
Received: 30 October 2021 / Revised: 7 January 2022 / Accepted: 11 January 2022 / Published: 15 January 2022
(This article belongs to the Collection Emerging Cancer Target Genes)
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. View Full-Text
Keywords: multiple myeloma; chronic hypoxia; asparaginyl endopepdidase (AEP); legumain; glycolysis multiple myeloma; chronic hypoxia; asparaginyl endopepdidase (AEP); legumain; glycolysis
Show Figures

Figure 1

MDPI and ACS Style

Clees, A.-S.; Stolp, V.; Häupl, B.; Fuhrmann, D.C.; Wempe, F.; Seibert, M.; Weber, S.; Banning, A.; Tikkanen, R.; Williams, R.; Brüne, B.; Serve, H.; Schnütgen, F.; von Metzler, I.; Kurrle, N. Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene. Cells 2022, 11, 292. https://doi.org/10.3390/cells11020292

AMA Style

Clees A-S, Stolp V, Häupl B, Fuhrmann DC, Wempe F, Seibert M, Weber S, Banning A, Tikkanen R, Williams R, Brüne B, Serve H, Schnütgen F, von Metzler I, Kurrle N. Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene. Cells. 2022; 11(2):292. https://doi.org/10.3390/cells11020292

Chicago/Turabian Style

Clees, Ada-Sophia, Verena Stolp, Björn Häupl, Dominik C. Fuhrmann, Frank Wempe, Marcel Seibert, Sarah Weber, Antje Banning, Ritva Tikkanen, Richard Williams, Bernhard Brüne, Hubert Serve, Frank Schnütgen, Ivana von Metzler, and Nina Kurrle. 2022. "Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene" Cells 11, no. 2: 292. https://doi.org/10.3390/cells11020292

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop