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Schwann cells shape the neuro-immune environs and control cancer progression

  • German V. Martyn
  • Galina V. Shurin
  • Anton A. Keskinov
  • Yuri L. Bunimovich
  • Michael R. ShurinEmail author
Focussed Research Review

Abstract

At present, significant experimental and clinical data confirm the active involvement of the peripheral nervous system (PNS) in different phases of cancer development and progression. Most of the research effort focuses on the impact of distinct neuronal types, e.g., adrenergic, cholinergic, dopaminergic, etc. in carcinogenesis, generally ignoring neuroglia. The very fact that these cells far outnumber the other cellular types may also play an important role worthy of study in this context. The most prevalent neuroglia within the PNS consists of Schwann cells (SCs). These cells play a substantial role in maintaining homeostasis within the nervous system. They possess distinct immunomodulatory, inflammatory and regenerative capacities—also, one should consider their broad distribution throughout the body; this makes them a perfect target for malignant cells during the initial stages of cancer development and the very formation of the tumor microenvironment itself. We show that SCs in the tumor milieu attract different subsets of immune regulators and augment their ability to suppress effector T cells. SCs may also up-regulate invasiveness of tumor cells and support metastatic disease. We outline the interactive potential of SCs juxtaposed with cancerous cells, referring to data from various external sources alongside data of our own.

Keywords

Schwann cells Cancer Neuroglia Tumor microenvironment MDSC PIVAC 18 

Abbreviations

CNS

Central nervous system

DFTD

Devil facial tumor disease

DRG

Dorsal root ganglion

EMT

Epithelial–mesenchymal transition

GM-CSF

Granulocyte–macrophage colony-stimulating factor

HMGB1

High-mobility group box 1

MAG

Myelin-associated glycoprotein

MDSC

Myeloid-derived suppressor cell(s)

MET

Mesenchymal–epithelial transition

NB

Neuroblastoma

Nrg

Neuregulin

PGP 9.5

Protein gene product 9.5

PNI

Perineural invasion

PNS

Peripheral nervous system

SC

Schwann cell(s)

SDF-1α

Stromal cell-derived factor 1 (CXCL12)

SPARC

Secreted protein acidic and rich in cysteine

TµE

Tumor microenvironment

Notes

Funding

This work was supported by London Foundation Grant (to M. R. Shurin) and University of Pittsburgh Cancer Institute (UPCI) Melanoma and SPORE in Skin Cancer Career Enhancement Program Award NIH P50CA121973 (to Y. L. Bunimovich).

Author contributions

Conceptualization, MRS, AAK and YLB; Methodology, GVS, and MRS; Investigation, GVS and YLB; Writing —Original Draft, GVM and MRS; Writing—Review and Editing, GVM and MRS; Funding Acquisition, MRS and YLB; Resources, MRS and AAK; Supervision, GVS and MRS.

Compliance with ethical standards

Conflict of interest

The author reports no conflicts of interest in this work.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • German V. Martyn
    • 1
  • Galina V. Shurin
    • 2
  • Anton A. Keskinov
    • 5
  • Yuri L. Bunimovich
    • 4
  • Michael R. Shurin
    • 2
    • 3
    • 6
    Email author
  1. 1.Department of NeurologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  2. 2.Department of PathologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  3. 3.Department of ImmunologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  4. 4.Department of DermatologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  5. 5.Centre for Strategic Planning and Management of Biomedical Health RisksMinistry of HealthMoscowRussia
  6. 6.Clinical ImmunopathologyUniversity of Pittsburgh Medical CenterPittsburghUSA

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