A Defined, Controlled Culture System for Primary Bovine Chromaffin Progenitors Reveals Novel Biomarkers and Modulators

Masjkur, Jimmy; Levenfus, Ian; Lange, Sven M.; Arps-Forker, Carina; Poser, Steven; Qin, Nan; Vukićević, Vladimir; Chavakis, Triantafyllos; Eisenhofer, Graeme; Bornstein, Stefan R.; Ehrhart‐Bornstein, Monika; Androutsellis-Theotokis, Andreas

doi:10.5966/sctm.2013-0211

Cited by 8 publications

(8 citation statements)

References 31 publications

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“…Oligodendrocyte progenitors also express HES3 in the adult mammalian brain (38). Beyond the brain, HES3+ cells are also found in the pancreas (a significant percentage of b-cells express HES3) (34,43) and the adrenal gland [HES3 expression has been reported in adrenomedullary chromaffin progenitors of the medulla and the zona glomerulosa of the adrenal cortex, where cortical stem cells are thought to reside (35,44)].…”

Section: Roles Of Hes3 In Regeneration and Cancermentioning

confidence: 99%

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

et al. 2019

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Cancer cells can switch between signaling pathways to regulate growth under different conditions. In the tumor microenvironment, this likely helps them evade therapies that target specific pathways. We must identify all possible states and utilize them in drug screening programs. One such state is characterized by expression of the transcription factor Hairy and Enhancer of Split 3 (HES3) and sensitivity to HES3 knockdown, and it can be modeled in vitro. Here, we cultured 3 primary human brain cancer cell lines under 3 different culture conditions that maintain low, medium, and high HES3 expression and characterized gene regulation and mechanical phenotype in these states. We assessed gene expression regulation following HES3 knockdown in the HES3‐high conditions. We then employed a commonly used human brain tumor cell line to screen Food and Drug Administration (FDA)‐approved compounds that specifically target the HES3‐high state. We report that cells from multiple patients behave similarly when placed under distinct culture conditions. We identified 37 FDA‐approved compounds that specifically kill cancer cells in the high‐HES3–expression conditions. Our work reveals a novel signaling state in cancer, biomarkers, a strategy to identify treatments against it, and a set of putative drugs for potential repurposing.—Poser, S. W., Otto, O., Arps‐Forker, C., Ge, Y., Herbig, M., Andree, C., Gruetzmann, K., Adasme, M. F., Stodolak, S., Nikolakopoulou, P., Park, D. M., Mcintyre, A., Lesche, M., Dahl, A., Lennig, P., Bornstein, S. R., Schroeck, E., Klink, B., Leker, R. R., Bickle, M., Chrousos, G. P., Schroeder, M., Cannistraci, C. V., Guck, J., Androutsellis‐Theotokis, A. Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery. FASEB J. 33, 9235–9249 (2019). http://www.fasebj.org

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Section: Roles Of Hes3 In Regeneration and Cancermentioning

confidence: 99%

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

et al. 2019

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“…We have for the first time been able to prove the existence of proliferation and differentiation-competent sympathoadrenal progenitor cells within the adult adrenal medulla and have established methods for their isolation from bovine (Chung et al, 2009;Ehrhart-Bornstein et al, 2010;Masjkur et al, 2014) and human (Santana et al, 2012) adrenals. Under low-attachment cell culture conditions, where adherence to the culture dish is prevented, these cells express progenitor markers, have in vitro self-renewing capacity and grow in spheres, which we called chromospheres.…”

Section: Chromaffin Progenitor Cellsmentioning

confidence: 99%

Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation?

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Androutsellis-Theotokis

et al. 2017

Molecular and Cellular Endocrinology

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“…Aspects of this pathway are not limited to NSCs but can be found in a number of plastic cell types, including putative cancer stem cells from glioblastoma multiforme patients and chromaffin progenitor cells from the bovine adrenal medulla (78,79). STAT3-Ser has been shown to drive carcinogenesis in models of prostate cancer (80).…”

Section: Notch Signaling In Neural Developmentmentioning

confidence: 99%

Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology

et al. 2016

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Loss of insulin-producing pancreatic islet β-cells is a hallmark of type 1 diabetes. Several experimental paradigms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these pathways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling pathways should not be seen as “on” or “off” but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play important roles. Thus, a pathway, once considered as “off” or “low” may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A formidable source of noncanonical signal transduction concepts is neural stem cells because these cells appear to have acquired unusual signaling interpretations to allow them to maintain their unique dual properties (self-renewal and multipotency). We discuss how such findings from the neural field can provide a blueprint for the identification of new molecular mechanisms regulating pancreatic biology, with a focus on Notch, Hes/Hey, and hedgehog pathways.

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A Defined, Controlled Culture System for Primary Bovine Chromaffin Progenitors Reveals Novel Biomarkers and Modulators

Cited by 8 publications

References 31 publications

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery

Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation?

Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology

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