Factors Within the Endoneurial Microenvironment Act to Suppress Tumorigenesis of MPNST

Front. Cell. Neurosci., 2018 · DOI: 10.3389/fncel.2018.00356 · Published: October 11, 2018

Simple Explanation

This study investigates how the environment within nerves affects the growth of nerve tumors called malignant peripheral nerve sheath tumors (MPNST). The goal is to find ways to control these tumors without damaging the nerves themselves. Researchers created tumor-like cells from nerve cells and transplanted them into different areas of the body. They found that when these cells were placed inside a specific part of the nerve (endoneurium), their growth was significantly slowed down. Further analysis revealed that a specific factor, ciliary neurotrophic factor (CNTF), found in the endoneurium, could stop these tumor-like cells from growing. This suggests CNTF could be a potential treatment for MPNST.

Study Duration

2-4 Months

Participants

Adult Sprague Dawley rats and immune-deficient Foxn1nu, NOD/CB17-Prkdcscid/NcrCrl mice

Evidence Level

Not specified

Key Findings

1
Adult rodent Schwann cells can be induced to form MPNST-like tumors after transplantation.
2
The endoneurial compartment within the peripheral nerve is a unique microenvironment enriched in tumor suppressive factors.
3
CNTF can block proliferation of iSCs mimicking the inhibition observed when grafted iSCs are contained within the endoneurial compartment in vivo.

Research Summary

This study developed a reproducible in vitro model to study MPNST from isolated adult Schwann cells (iSCs) that following transplantation, share striking phenotypic resemblance to primary human MPNST tumors. The results underscore the importance of regional microenvironments in promoting tumorigenic growth and identify the endoneurial compartment within the peripheral nerve as a unique microenvironment enriched in tumor suppressive factors. By probing uniquely expressed proteins within the endoneurial compartment, the study demonstrated an autonomous role for CNTF to block proliferation of iSCs mimicking the inhibition observed when grafted iSCs are contained within the endoneurial compartment in vivo.

Practical Implications

Therapeutic Development

CNTF or small molecules targeting its downstream targets, may offer some therapeutic value toward controlling aberrant Schwann cells and MPNSTs.

Understanding Microenvironment

The cellular microenvironment plays a key role in predictability of tumor formation, offering new avenues for research and potential therapeutic interventions.

Safety of Cell Therapies

A cautionary note regarding the use of adult Schwann cells for stem cell transplant-based therapies due to genomic instability.

Study Limitations

1
Identified genes only partially accounted for the progression of benign tumors toward high-grade PNST formation.
2
Additional contributors, such as, epigenetic and environmental factors, must also play a role in MPNST development.
3
Further study is needed to elucidate the precise mechanisms of CNTF-induced cell cycle arrest in iSCs.

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