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

Abstract

Adult Schwann cells (SCs) possess an inherent plastic potential. This plasticity allows SCs to acquire repair-specific functions essential for peripheral nerve regeneration. Here, we investigate whether stromal SCs in benign-behaving peripheral neuroblastic tumors adopt a similar cellular state. We profile ganglioneuromas and neuroblastomas, rich and poor in SC stroma, respectively, and peripheral nerves after injury, rich in repair SCs. Indeed, stromal SCs in ganglioneuromas and repair SCs share the expression of nerve repair-associated genes. Neuroblastoma cells, derived from aggressive tumors, respond to primary repair-related SCs and their secretome with increased neuronal differentiation and reduced proliferation. Within the pool of secreted stromal and repair SC factors, we identify EGFL8, a matricellular protein with so far undescribed function, to act as neuritogen and to rewire cellular signaling by activating kinases involved in neurogenesis. In summary, we report that human SCs undergo a similar adaptive response in two patho-physiologically distinct situations, peripheral nerve injury and tumor development.

Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function

“…Kinase-substrate enrichment analysis was performed on site-centric quantification data obtained via MaxQuant data processing as previously described (Weiss et al 2021 ). Search parameters were adjusted to additional dynamic modification of phosphorylation of serine, threonine and tyrosine.…”

Landscape of Bone Marrow Metastasis in Human Neuroblastoma Unraveled by Transcriptomics and Deep Multiplex Imaging

“…As neuroblastoma displays substantial genetic heterogeneity, most prominently heterogeneous amplification of the oncogenic driver MYCN [5,100], and since FAIM2 expression was associated with MYCNamplification status in tumors, but not DTCs, it will be important to evaluate the correlation of genetic and phenotypic heterogeneity. Especially as in response to chemotherapy or molecules inducing neuronal differentiation, such as retinoic acid or neurotrophins, tumor cells can overcome MYCN-driven differentiation blocks, undergo apoptosis or cellular senescence [37,[101][102][103][104]. Moreover, our findings represent a valuable source of information for the design of therapeutic approaches depending on the distribution of target molecules on cancer cells, such as immunotherapies [105], and can hence contribute towards better patient stratification in neuroblastoma.…”

SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7

“…1F, G ). SAPCD2 was also found to be significantly highly expressed in NB in comparison to ganglioneuroma (GN), the benign representative of peripheral neuroblastic tumors, by analyzing a recent study [ 16 ] which performed RNA-Seq on GN and NB samples (Supplementary Fig. S1 ).…”