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Cancer Res. 2019 May 15;79(10):2736-2747. doi: 10.1158/0008-5472.CAN-18-3872. Epub 2019 Mar 26.

Melanoma-Induced Reprogramming of Schwann Cell Signaling Aids Tumor Growth.

Author information

1
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
2
Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
3
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
4
Hillman Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
5
Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
6
Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. bunimovichyl@upmc.edu.
#
Contributed equally

Abstract

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.

PMID:
30914431
PMCID:
PMC6522315
[Available on 2020-05-15]
DOI:
10.1158/0008-5472.CAN-18-3872

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