JunB is a key regulator of multiple myeloma bone marrow angiogenesis

Autor: Martin Pecherstorfer, Heng Mei, Yu Hu, Klaus Podar, Chunyan Sun, Judith Lind, Martin Sattler, Qinyue Jiang, Fengjuan Fan, Erwin F. Wagner, Eugenio Morelli, Anja Seckinger, Sonia Vallet, Stefano Malvestiti, Latifa Bakiri, Andreas Stadlbauer, Giovanni Tonon, Hartmut Goldschmidt, Dirk Jaeger, Jose Manuel Garcia-Manteiga, Dirk Hose, Pierfrancesco Tassone
Přispěvatelé: Hematology, Basic (bio-) Medical Sciences
Rok vydání: 2021
Předmět:
Vascular Endothelial Growth Factor A
key regulator
0301 basic medicine
Vascular Endothelial Growth Factor B
Cancer Research
JUNB
Angiogenesis
Primary Cell Culture
bone marrow angiogenesis
Regulator
Myeloma
Mice
SCID
Biology
Article
Mice
03 medical and health sciences
0302 clinical medicine
Bone Marrow
Mice
Inbred NOD
Cell Line
Tumor
hemic and lymphatic diseases
medicine
Animals
Humans
Insulin-Like Growth Factor I
Transcription factor
Multiple myeloma
Gene knockdown
Neovascularization
Pathologic
Interleukin-6
Correction
Hematology
medicine.disease
3. Good health
multiple myeloma
Vascular endothelial growth factor B
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Cancer research
Heterografts
Female
Bone marrow
JunB
Transcription Factors
Cell signalling
Zdroj: Leukemia
ISSN: 1476-5551
0887-6924
Popis: 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.
Databáze: OpenAIRE
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