3D-Dynamic Culture Models of Multiple Myeloma

Ferrarini, Marina; Steimberg, Nathalie; Boniotti, Jennifer; Berenzi, Angiola; Belloni, Daniela; Mazzoleni, Giovanna; Ferrero, Elisabetta

doi:10.1007/978-1-4939-7021-6_13

Cited by 11 publications

(11 citation statements)

References 18 publications

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“…Innovative 3D co-culture models replicate BM-specific structural features and closely recreate functional tumor-stroma cell and -extracellular matrix interactions [ 60 , 61 ]. They therefore evolve as concise surrogates of the MM BM microenvironment.…”

Section: Resultsmentioning

confidence: 99%

JunB is a key regulator of multiple myeloma bone marrow angiogenesis

et al. 2021

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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.

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Section: Resultsmentioning

confidence: 99%

JunB is a key regulator of multiple myeloma bone marrow angiogenesis

et al. 2021

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“…2A) has emerged as an optimal tissue culture device: specifically, its ability to guarantee gas/nutrient supply and waste elimination (mass transfer) results in preservation of cell viability and tissue integrity within large 3D cell/tissue masses. [79][80][81] Culture of ECD tissues, obtained for diagnostic purposes, in bioreactor revealed that CD68 + histiocytes retained constitutive ERK phosphorylation ( Fig. 2B) and the capability to secrete prototypical cytokines and chemokines; both features were reverted upon BRAF inhibition with vemurafenib.…”

Section: Ecd Histiocytes Undergo Mutation-driven Metabolic Reprogrammingmentioning

confidence: 99%

“…The microgravity‐based Rotary Cell Culture System (RCCS™, Synthecon Inc., USA) bioreactor (Fig. 2A) has emerged as an optimal tissue culture device: specifically, its ability to guarantee gas/nutrient supply and waste elimination (mass transfer) results in preservation of cell viability and tissue integrity within large 3D cell/tissue masses 79‐81 . Culture of ECD tissues, obtained for diagnostic purposes, in bioreactor revealed that CD68 + histiocytes retained constitutive ERK phosphorylation (Fig.…”

Section: Ecd Pathogenesis: At the Crossroad Between Inflammation And mentioning

confidence: 99%

Erdheim-Chester disease: An in vivo human model of Mϕ activation at the crossroad between chronic inflammation and cancer

Cavalli

Dagna

Biavasco

et al. 2020

Journal of Leukocyte Biology

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Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by infiltration of multiple tissues by CD68 + foamy M s (or 'histiocytes'). Clinical manifestations arise from mass-forming lesions or from tissue and systemic inflammation. ECD histiocytes harbor oncogenic mutations along the MAPK-kinase signaling pathway (BRAF V600E in more than half of the patients), and secrete abundant pro-inflammatory cytokines and chemokines. Based on these features, ECD is considered an inflammatory myeloid neoplasm, and is accordingly managed with targeted kinase inhibitors or immunosuppressive and cytokine-blocking agents. Evidence is emerging that maladaptive metabolic changes, particularly up-regulated glycolysis, represent an additional, mutation-driven feature of ECD histiocytes, which sustains deregulated and protracted proinflammatory activation and cytokine production. Besides translational relevance to the management of ECD patients and to the development of new therapeutic approaches, recognition of ECD as a natural human model of chronic, maladaptive M activation instructs the understanding of M dysfunction in other chronic inflammatory conditions.

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“…Another one consists of the incorporation of the vascular/lymphatic network simulating dynamic blood flow and providing the mechanical signals regulating tumor development and function. An increasing number of studies report the development of such perfusion systems applied to models of various primary and metastatic tumor types [20,[246][247][248][249].…”

Section: Perspectives and Future Directionsmentioning

confidence: 99%

Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors

Roy

Magne

Vaillancourt-Audet

et al. 2020

BioMed Research International

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Cancer research has considerably progressed with the improvement of in vitro study models, helping to understand the key role of the tumor microenvironment in cancer development and progression. Over the last few years, complex 3D human cell culture systems have gained much popularity over in vivo models, as they accurately mimic the tumor microenvironment and allow high-throughput drug screening. Of particular interest, in vitrohuman 3D tissue constructs, produced by the self-assembly method of tissue engineering, have been successfully used to model the tumor microenvironment and now represent a very promising approach to further develop diverse cancer models. In this review, we describe the importance of the tumor microenvironment and present the existing in vitro cancer models generated through the self-assembly method of tissue engineering. Lastly, we highlight the relevance of this approach to mimic various and complex tumors, including basal cell carcinoma, cutaneous neurofibroma, skin melanoma, bladder cancer, and uveal melanoma.

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3D-Dynamic Culture Models of Multiple Myeloma

Cited by 11 publications

References 18 publications

JunB is a key regulator of multiple myeloma bone marrow angiogenesis

JunB is a key regulator of multiple myeloma bone marrow angiogenesis

Erdheim-Chester disease: An in vivo human model of Mϕ activation at the crossroad between chronic inflammation and cancer

Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors

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