JunB is a key regulator of multiple myeloma bone marrow angiogenesis.

Animals Bone Marrow / blood supply Cell Line, Tumor Female Heterografts Humans Insulin-Like Growth Factor I / metabolism Interleukin-6 / metabolism Mice Mice, Inbred NOD Mice, SCID Multiple Myeloma / blood supply Neovascularization, Pathologic / genetics Primary Cell Culture Transcription Factors / genetics Vascular Endothelial Growth Factor A / metabolism Vascular Endothelial Growth Factor B / metabolism

Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
12 2021
Historique:
received: 14 12 2020
accepted: 28 04 2021
revised: 14 04 2021
pubmed: 20 5 2021
medline: 29 1 2022
entrez: 19 5 2021
Statut: ppublish

Résumé

Bone marrow (BM) angiogenesis significantly influences disease progression in multiple myeloma (MM) patients and correlates with adverse prognosis. The present study shows a statistically significant correlation of the AP-1 family member JunB with VEGF, VEGFB, and IGF1 expression levels in MM. In contrast to the angiogenic master regulator Hif-1α, JunB protein levels were independent of hypoxia. Results in tumor-cell models that allow the induction of JunB knockdown or JunB activation, respectively, corroborated the functional role of JunB in the production and secretion of these angiogenic factors (AFs). Consequently, conditioned media derived from MM cells after JunB knockdown or JunB activation either inhibited or stimulated in vitro angiogenesis. The impact of JunB on MM BM angiogenesis was finally confirmed in a dynamic 3D model of the BM microenvironment, a xenograft mouse model as well as in patient-derived BM sections. In summary, in continuation of our previous study (Fan et al., 2017), the present report reveals for the first time that JunB is not only a mediator of MM cell survival, proliferation, and drug resistance, but also a promoter of AF transcription and consequently of MM BM angiogenesis. Our results thereby underscore worldwide efforts to target AP-1 transcription factors such as JunB as a promising strategy in MM therapy.

Identifiants

DOI: 10.1038/s41375-021-01271-9 PMID: 34007044 PMC: PMC8632680
pubmed: 34007044
doi: 10.1038/s41375-021-01271-9
pii: 10.1038/s41375-021-01271-9
pmc: PMC8632680
doi:

Substances chimiques

IGF1 protein, human 0
IL6 protein, human 0
Interleukin-6 0
JunB protein, human 0
Transcription Factors 0
VEGFA protein, human 0
VEGFB protein, human 0
Vascular Endothelial Growth Factor A 0
Vascular Endothelial Growth Factor B 0
Insulin-Like Growth Factor I 67763-96-6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3509-3525

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

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Auteurs

Fengjuan Fan (F)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany.
ORCID: 0000-0001-8727-5258

Stefano Malvestiti (S)

Department of Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany.

Sonia Vallet (S)

Department of Internal Medicine II, University Hospital Krems, Krems an der Donau, Austria.
Molecular Oncology and Hematology Unit, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria.

Judith Lind (J)

Molecular Oncology and Hematology Unit, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria.

Jose Manuel Garcia-Manteiga (JM)

Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Eugenio Morelli (E)

Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-8850-0442

Qinyue Jiang (Q)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Anja Seckinger (A)

University Hospital Heidelberg, Heidelberg, Germany.
Laboratory of Hematology and Immunology & Laboratory for Myeloma Research, Vrije Universiteit Brussel (VUB) Belgium, Brussels, Belgium.

Dirk Hose (D)

University Hospital Heidelberg, Heidelberg, Germany.
Laboratory of Hematology and Immunology & Laboratory for Myeloma Research, Vrije Universiteit Brussel (VUB) Belgium, Brussels, Belgium.

Hartmut Goldschmidt (H)

Department of Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany.
University Hospital Heidelberg, Heidelberg, Germany.
ORCID: 0000-0003-0961-0035

Andreas Stadlbauer (A)

Department of Neurosurgery, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Institute of Medical Radiology, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria.
ORCID: 0000-0001-8348-2620

Chunyan Sun (C)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Heng Mei (H)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
ORCID: 0000-0001-7941-2443

Martin Pecherstorfer (M)

Department of Internal Medicine II, University Hospital Krems, Krems an der Donau, Austria.

Latifa Bakiri (L)

Genes & Disease Group, Department of Dermatology, Medical University of Vienna (MUW), Vienna, Austria.
ORCID: 0000-0002-6300-2420

Erwin F Wagner (EF)

Genes & Disease Group, Department of Dermatology, Medical University of Vienna (MUW), Vienna, Austria.
Genes & Disease Group, Department of Laboratory Medicine, Medical University of Vienna (MUW), Vienna, Austria.
ORCID: 0000-0001-7872-0196

Giovanni Tonon (G)

Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Functional Genomics of Cancer Unit, Experimental Oncology Division, IRCCS San Raffaele Scientific Institute, Milan, Italy.
ORCID: 0000-0003-2973-5038

Martin Sattler (M)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Yu Hu (Y)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. dr_huyu@126.com.
ORCID: 0000-0002-2815-4568

Pierfrancesco Tassone (P)

Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.

Dirk Jaeger (D)

Department of Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany.

Klaus Podar (K)

Department of Medical Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany. klaus.podar@krems.lknoe.at.
Department of Internal Medicine II, University Hospital Krems, Krems an der Donau, Austria. klaus.podar@krems.lknoe.at.
Molecular Oncology and Hematology Unit, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria. klaus.podar@krems.lknoe.at.
ORCID: 0000-0002-7414-3632

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questionsmedicales.fr › Eucaryotes › Animaux › JunB is a key regulator of multiple myeloma...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Moelle osseuse › JunB is a key regulator of multiple myeloma...
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