January 2022 - Tamara Weiss and Sabine Taschner-Mandl

Mag. Tamara Weiss, PhD and Dr. Sabine Taschner-Mandl

MedUni Wien RESEARCHER OF THE MONTH January 2022

Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8

In this study, we unfolded the versatile nature of Schwann cells, a cell type present in peripheral nerves, but also found in the stroma of benign peripheral neuroblastic tumors. The physiological function of Schwann cells ensures the correct development and maintenance of axons in the peripheral nervous system. In response to nerve injury, Schwann cells activate a repair-mode to support the regeneration of nerve cells. However, the role of stromal Schwann cells in peripheral neuroblastic tumors remained obscure. We therefore compared the cellular state of stromal Schwann cells in tumors and repair Schwann cells in injured nerves. Our results revealed that stromal are unexpectedly similar to repair Schwann cells and thus, are capable of exerting repair-associated functions that shape an anti-tumor microenvironment. Furthermore, stromal SCs produce EGFL8, a signaling factor with so far elusive function. EGFL8 is able to induce neuronal differentiation and reduce the aggressiveness of neuroblastic tumor cells. These findings encourage the exploitation of SC derived signaling factors such as EGFL8 in therapeutic approaches for aggressive peripheral neuroblastic tumors and peripheral nerve injury.

Selected Literature

1. Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8. Weiss T, Taschner-Mandl S, Janker L, Bileck A, Rifatbegovic F, Kromp F, Sorger H, Kauer MO, Frech C, Windhager R, Gerner C, Ambros PF, Ambros IM. (2021) NATURE COMMUNICATIONS, 2021 Mar 12;12(1):1624. doi: 10.1038/s41467-021-21859-0. PMID: 33712610; PMCID: PMC7954855.
2. Landscape of Bone Marrow Metastasis in Human Neuroblastoma Unraveled by Transcriptomics and Deep Multiplex Imaging. Lazic D, Kromp F, Rifatbegovic F, Repiscak P, Kirr M, Mivalt F, Halbritter F, Bernkopf M, Bileck A, Ussowicz M, Ambros I M, Ambros, P F, Gerner C, Ladenstein R, Ostalecki C, Taschner-Mandl S. (2021)  Cancers. 13(17):4311. https://doi.org/10.3390/cancers13174311  
3.  Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden. Peneder P, Stütz A M, Surdez D, Krumbholz M, Semper S, Chicard M, Sheffield N C, Pierron G, Lapouble E, Tötzl M, Ergüner B, Barreca D, Rendeiro A F, Agaimy A, Boztug H, Engstler G, Dworzak M, Bernkopf M, Taschner-Mandl S, Ambros I M, Myklebost O, Marec-Bérard P, Burchill S A, Brennan B, Strauss S J, Whelan J, Schleiermacher G, Schaefer C, Dirksen U, Hutter C, Boye K, Ambros P F, Delattre O, Metzler M, Bock C, Tomazou E M. (2021) NATURE COMMUNICATIONS, May 28;12(1):3230. doi: 10.1038/s41467-021-23445-w.
4. Defining the regenerative effects of native spider silk fibers on primary Schwann cells, sensory neurons, and nerve-associated fibroblasts. Millesi F, Weiss T, Mann A, Haertinger M, Semmler L, Supper P, Pils D, Naghilou A, Radtke C. (2020) FASEB J. doi: 10.1096/fj.202001447R. Epub 2020 Nov 19. PMID: 33210360.
5. An annotated fluorescence image dataset for training nuclear segmentation methods. Kromp F, Bozsaky E, Rifatbegovic F, Fischer L, Ambros M, Berneder M, Weiss T, Lazic D, Dörr W, Hanbury A, Beiske K, Ambros P F, Ambros I M & Taschner-Mandl S (2020). NATURE SCIENTIFIC DATA, 7(1), 262. https://doi.org/10.1038/s41597-020-00608-w
6. Assessment of Pre-Analytical Sample Handling Conditions for Comprehensive Liquid Biopsy Analysis. Gerber T, Taschner-Mandl S, Saloberger-Sindhoringer L, Popitsch N, Heitzer E, Witt V, Geyeregger R, Hutter C, Schwentner R, Ambros I A, and Ambros P F (2020) J Mol Diagn. https://doi.org/10.1016/j.jmoldx.2020.05.006
7. Automated image analysis of stained cytospins to quantify Schwann cell purity and proliferation. Weiss T, Semmler L, Millesi F, Mann A, Haertinger M, Salzmann M, Radtke C. (2020) PLOS ONE, May 22;15(5):e0233647. doi: 10.1371/journal.pone.0233647.
8. Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization. Haertinger M, Weiss T, Mann A, Tabi A, Brandel V, Radtke C. (2020) CELLS. Jan 9;9(1). pii: E163.
9. Metronomic topotecan impedes tumor growth of MYCN-amplified neuroblastoma cells in vitro and in vivo by therapy induced senescence. Taschner-Mandl S, Schwarz M, Blaha J, Kauer M, Kromp F, Frank N, Rifatbegovic F, Weiss T, Ladenstein R, Hohenegger M, Ambros IM, Ambros PF. (2016) ONCOTARGET, 7: 3571-3586
10. Proteomics and transcriptomics of peripheral nerve tissue and cells unravel new aspects of the human Schwann cell repair phenotype. Weiss T, Taschner-Mandl S, Bileck A, Slany A, Kromp F, Rifatbegovic F, Frech C, Windhager R, Kitzinger H, Tzou CH, Ambros PF, Gerner C, Ambros IM. (2016) GLIA, 64: 2133-2153