How Schwann cells facilitate cancer progression in nerves

Deborde, Sylvie; Wong, Richard J.

doi:10.1007/s00018-017-2578-x

Cited by 83 publications

(103 citation statements)

References 149 publications

(218 reference statements)

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“…While the number of investigations into the neuronal regulation of cancer has increased in recent years, the involvement of the peripheral neuroglia in cancer progression remains poorly understood (11,12). Schwann cells (SC) comprise the majority of the neuroglia of the PNS and are intimately associated with the nerve fibers, providing trophic support and a signaling scaffold for the axon (13,14).…”

Section: Introductionmentioning

confidence: 99%

Melanoma-Induced Reprogramming of Schwann Cell Signaling Aids Tumor Growth

et al. 2019

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The tumor microenvironment has been compared with a nonhealing wound involving a complex interaction between multiple cell types. Schwann cells, the key regulators of peripheral nerve repair, have recently been shown to directly affect nonneural wound healing. Their role in cancer progression, however, has been largely limited to neuropathic pain and perineural invasion. In this study, we showed that melanoma activated otherwise dormant functions of Schwann cells aimed at nerve regeneration and wound healing. Such reprogramming of Schwann cells into repair-like cells occurred during the destruction and displacement of neurons as the tumor expanded and via direct signaling from melanoma cells to Schwann cells, resulting in activation of the nerve injury response. Melanoma-activated Schwann cells significantly altered the microenvironment through their modulation of the immune system and the extracellular matrix in a way that promoted melanoma growth in vitro and in vivo. Local inhibition of Schwann cell activity following cutaneous sensory nerve transection in melanoma orthotopic models significantly decreased the rate of tumor growth. Tumor-associated Schwann cells, therefore, can have a significant protumorigenic effect and may present a novel target for cancer therapy.Significance: These findings reveal a role of the nerve injury response, particularly through functions of activated Schwann cells, in promoting melanoma growth. Recently, similar activation of the peripheral glia was described in

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Section: Introductionmentioning

confidence: 99%

Melanoma-Induced Reprogramming of Schwann Cell Signaling Aids Tumor Growth

et al. 2019

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“…23 So, some scholars speculated that Schwann-like cell differentiation of tumor cells might be one of the mechanisms of PNI occurrence in tumors. 24,25 In the SACC specimens, Shan et al 17 found that the expression of S100A4 and GFAP around the nerve was distinctly enhanced. However, the relationship between MIF and Schwann-like cell differentiation of tumor cells in PNI of SACC remained unknown.…”

Section: Introductionmentioning

confidence: 99%

MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma

Zhang

Wang

et al. 2019

Molecular Carcinogenesis

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Macrophage migration inhibitory factor (MIF) is a prominent orchestrator during the onset and progression of cancer. Recently, MIF was detected in salivary adenoid cystic carcinoma (SACC). However, its functional effect in perineural invasion (PNI) of SACC remained unknown. To illuminate the effect of MIF in genesis of PNI in SACC, we examined the expression of MIF, epithelial‐to‐mesenchymal transition (EMT)‐related markers, and Schwann cell markers by immunohistochemical analysis in 158 cases of SACC samples. Meanwhile, the correlation between MIF and PNI of SACC species was analyzed. Our data indicated that MIF expression was associated with PNI of SACC significantly. In vitro, the silence and overexpression experiments of MIF were performed in SACC cell lines. The ability of migration, invasion and PNI could be inhibited significantly by siRNA‐mediated MIF silence, and the occurrence of EMT and Schwann‐like cell differentiation was also inhibited by MIF silence in SACC‐LM cells. Overexpression of MIF in SACC‐83 cells using expressive plasmid showed the opposite effects. Our findings identified that an association between PNI and MIF expression existed. MIF may promote PNI of SACC by participating in cytoskeletal reorganization and pseudo foot formation induced by EMT and the Schwann‐like cell differentiation of SACC cells.

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“…The plastic potential of SCs is a double-edged sword. While essential for nerve repair, recent studies point out its adverse effect in neuropathies and epithelial cancer progression (Deborde & Wong, 2017;Horste et al, 2010). Here, we demonstrate a favorable impact of SC plasticity on peripheral neuroblastic tumor cells as it manifests in SC stroma during the development of benignly behaving GNB/GN.…”

Section: Exploiting Schwann Cell Plasticity In Therapeutic Approachesmentioning

confidence: 99%

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

Weiss

Taschner‐Mandl

Bileck

et al. 2020

Preprint

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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 performed transcriptome profiling of human ganglioneuromas and neuroblastomas, rich and poor in SC-stroma, respectively, as well as human injured nerves, 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 stromal SCs underwent an adaptive response to neuroblastic tumor cells and exert repairassociated functions in the microenvironment resulting in a benign tumor development.Further, SC-derived factors, such as EGFL8, may be of therapeutic value for aggressive, SCstroma poor neuroblastomas. SYNOPSISIn order to investigate the nature of stromal Schwann cells in benign peripheral neuroblastic tumors (ganglioneuromas), we compared the cellular state of stromal Schwann cells with repair-associated Schwann cells emerging in peripheral nerves after injury. • Stromal Schwann cells in ganglioneuromas and repair Schwann cells in injured nervesshare the expression of nerve repair-associated genes.• Neuroblastoma cell lines, derived from high-risk metastatic peripheral neuroblastic tumors (neuroblastomas), respond to primary repair Schwann cells and their secretome with increased neuronal differentiation and reduced proliferation. • Stromal and repair Schwann cells express the matricellular protein EGFL8, which is capable to induce neuronal differentiation of neuroblastoma cell lines in recombinant form. Human Schwann Cell Plasticity Weiss, Taschner-Mandl et al Page 4 of 48 ABBREVIATIONS SC … Schwann cell NT … peripheral neuroblastic tumor NB … neuroblastoma GNB … ganglioneuroblatoma GN … ganglioneuroma RT … room temperature IF … immunofluorescence THE PAPER EXPLAINED ProblemIn response to peripheral nerve damage, Schwann cells (SCs) are able to transform into specialized repair cells essential for nerve cell regeneration. Our previous studies indicated that this reactive/adaptive potential of human SCs is not restricted to injured nerve cells but also emerges in response to peripheral neuroblastic tumor cells. The usually benign subtypes of peripheral neuroblastic tumors, i.e. ganglioneuroblastomas and ganglioneuromas, contain neuronal differentiating tumor cells and are pervaded by various portions of stromal SCs. Of note, the amount of stromal SCs correlates with a favorable tumor behavior and increased patient survival, whereas aggre...

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How Schwann cells facilitate cancer progression in nerves

Cited by 83 publications

References 149 publications

Melanoma-Induced Reprogramming of Schwann Cell Signaling Aids Tumor Growth

Melanoma-Induced Reprogramming of Schwann Cell Signaling Aids Tumor Growth

MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma

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

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