1. Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8
- Author
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Reinhard Windhager, Fikret Rifatbegovic, Christian Frech, Helena Sorger, Peter F. Ambros, Florian Kromp, Maximilian Kauer, Sabine Taschner-Mandl, Lukas Janker, Inge M. Ambros, Tamara Weiss, Andrea Bileck, and Christopher Gerner
- Subjects
Male ,0301 basic medicine ,Cellular differentiation ,Cell Plasticity ,General Physics and Astronomy ,Neuroblastoma ,0302 clinical medicine ,Peripheral Nerve Injuries ,Aged, 80 and over ,Multidisciplinary ,integumentary system ,Neurogenesis ,Matricellular protein ,Cell Differentiation ,Middle Aged ,Neuroblastic Tumor ,Schwann cell ,Cell biology ,medicine.anatomical_structure ,Mechanisms of disease ,Peripheral nerve injury ,Female ,tissues ,Adult ,EGF Family of Proteins ,Cell signaling ,Stromal cell ,Adolescent ,Science ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Young Adult ,03 medical and health sciences ,Embryonal neoplasms ,medicine ,Humans ,Aged ,Cell Proliferation ,Calcium-Binding Proteins ,General Chemistry ,Coculture Techniques ,Nerve Regeneration ,030104 developmental biology ,nervous system ,Schwann Cells ,Transcriptome ,Cancer in the nervous system ,030217 neurology & neurosurgery - 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., Schwann cells (SCs) can acquire a repair phenotype following nerve injury. Here, the authors show that stromal SCs in ganglioneuromas express nerve-repair genes. Importantly, neuroblastoma cells respond to repair-related SCs increasing neuronal differentiation and reducing proliferation via EGFL8.
- Published
- 2021