Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8
Tamara Weiss, Sabine Taschner-Mandl, Andrea Bileck, Fikret Rifatbegovic, Helena Sorger, Max Kauer, Christian Frech, Reinhard Windhager, Christopher Gerner, Peter F Ambros, Inge M Ambros
Received Date: 2nd April 20
The remarkable plasticity of Schwann cells (SCs) enables the acquisition of repair-specific functions essential for peripheral nerve regeneration. We hypothesized that this plastic potential is manifested in stromal SCs found within mostly benign-behaving peripheral neuroblastic tumors. To shed light on the cellular state and impact of stromal SCs, we combined transcriptome and proteome profiling of human ganglioneuromas and neuroblastomas, rich and poor in SC-stroma, respectively, as well as human injured nerve explants, rich in repair SCs. The results revealed a nerve repair-characteristic gene expression signature of stromal SCs. In turn, primary repair SCs had a pro-differentiating and anti-proliferative effect on aggressive neuroblastoma cell lines after direct and trans-well co-culture. Within the pool of secreted stromal/repair SC factors, we identified EGFL8, a matricellular protein with so far undescribed function, to induce neuronal differentiation of neuroblastoma cell lines. This study indicates that human SCs undergo a similar adaptive response in two patho-physiologically distinct situations, peripheral nerve injury and tumor development. This response is mediated by EGFL8 and other SC derived factors, which might be of therapeutic value for neuroblastic tumors and nerve regeneration.
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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.