Nerves in the Tumor Microenvironment: Origin and Effects.

Wenjun Wang,Jifan Hu,Jiuwei Cui,Lingyu Li,Chao Niu,Zhi Li,Naifei Chen

doi:10.3389/fcell.2020.601738

Abstract

Studies have reported the vital role of nerves in tumorigenesis and cancer progression. Nerves infiltrate the tumor microenvironment thereby enhancing cancer growth and metastasis. Perineural invasion, a process by which cancer cells invade the surrounding nerves, provides an alternative route for metastasis and generation of tumor-related pain. Moreover, central and sympathetic nervous system dysfunctions and psychological stress-induced hormone network disorders may influence the malignant progression of cancer through multiple mechanisms. This reciprocal interaction between nerves and cancer cells provides novel insights into the cellular and molecular bases of tumorigenesis. In addition, they point to the potential utility of anti-neurogenic therapies. This review describes the evolving cross-talk between nerves and cancer cells, thus uncovers potential therapeutic targets for cancer.

Highlights

Cancer is among the leading causes of mortality
Accumulating evidence indicates that the nervous system participates in all stages of cancer, even in those that precede cancer development, such as pancreatic intraepithelial neoplasia (PanIN) or prostate intraepithelial neoplasia (PIN) (Magnon et al, 2013; Cole et al, 2015; Magnon, 2015; Saloman et al, 2016b; Kuol et al, 2018; Faulkner et al, 2019)
Nerve fibers that innervate normal tissues can be chemoattracted to tumor environments and outgrow as a result of neurotrophic factors that are released by the cancer cells

Summary

Introduction

Cancer is among the leading causes of mortality. Solid tumors are known to sculpt their microenvironment (e.g., molding angiogenesis pathways and forming pre-metastatic niches) in a bid to maximize their growth and metastatic potential (Magnon et al, 2013; Peinado et al, 2017). It is postulated that alterations in neurotrophic factor signaling before tumorigenesis can impact the progression from precancerous lesions to cancer by influencing tumor precursor cells and/or tissue innervation (Ayala et al, 2008). Nerve fibers that innervate normal tissues can be chemoattracted to tumor environments and outgrow as a result of neurotrophic factors that are released by the cancer cells.

Results

Conclusion