Journalartikel
Autorenliste: Clees, Ada-Sophia; Stolp, Verena; Häupl, Björn; Fuhrmann, Dominik C.; Wempe, Frank; Seibert, Marcel; Weber, Sarah; Banning, Antje; Tikkanen, Ritva; Williams, Richard; Brüne, Bernhard; Serve, Hubert; Schnütgen, Frank; von Metzler, Ivana; Kurrle, Nina
Jahr der Veröffentlichung: 2022
Zeitschrift: Cells
Bandnummer: 11
Heftnummer: 2
eISSN: 2073-4409
Open Access Status: Gold
DOI Link: https://doi.org/10.3390/cells11020292
Verlag: MDPI
Abstract:
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% O-2), 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.
Zitierstile
Harvard-Zitierstil: Clees, A., Stolp, V., Häupl, B., Fuhrmann, D., Wempe, F., Seibert, M., et al. (2022) Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene, Cells, 11(2), Article 292. https://doi.org/10.3390/cells11020292
APA-Zitierstil: Clees, A., Stolp, V., Häupl, B., Fuhrmann, D., Wempe, F., Seibert, M., Weber, S., Banning, A., Tikkanen, R., Williams, R., Brüne, B., Serve, H., Schnütgen, F., von Metzler, I., & Kurrle, N. (2022). Identification of the Cysteine Protease Legumain as a Potential Chronic Hypoxia-Specific Multiple Myeloma Target Gene. Cells. 11(2), Article 292. https://doi.org/10.3390/cells11020292
Schlagwörter
asparaginyl endopepdidase (AEP); BONE-MARROW; CHRONIC HYPOXIA; COLORECTAL-CANCER; GLYCOLYSIS; HEMATOPOIETIC STEM; legumain; LONG NONCODING RNA; multiple myeloma; PROGNOSTIC MARKER; PYRUVATE-KINASE
