Tumor Neurobiology and the War of Nerves in Cancer

Faulkner, Sam; Jobling, Phillip; March, Brayden; Jiang, Chen Chen; Hondermarck, Hubert

doi:10.1158/2159-8290.cd-18-1398

Cited by 181 publications

(163 citation statements)

References 81 publications

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“…In a seminal study, autonomic nerves were shown to have a critical role in the development and spread of prostate cancer and since this study, innervation has been shown to be an important component of the development of gastric, pancreatic and other cancers (Faulkner, Jobling, March, Jiang, & Hondermarck, 2019;Magnon et al, 2013). How tumors become innervated is unknown with most research focusing on the attraction of neurons and their potential regulation of the tumor microenvironment (Faulkner et al, 2019).…”

Section: Scs As Promoters Of Tissue Regenerationmentioning

confidence: 99%

Schwann cell plasticity‐roles in tissue homeostasis, regeneration, and disease

Stierli

Imperatore

Lloyd

2019

Glia

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How tissues are maintained over a lifetime and repaired following injury are fundamental questions in biology with a disruption to these processes underlying pathologies such as cancer and degenerative disorders. It is becoming increasingly clear that each tissue has a distinct mechanism to maintain homeostasis and respond to injury utilizing different types of stem/progenitor cell populations depending on the insult and/or with a contribution from more differentiated cells that are able to dedifferentiate to aid tissue regeneration. Peripheral nerves are highly quiescent yet show remarkable regenerative capabilities. Remarkably, there is no evidence for a classical stem cell population, rather all cell‐types within the nerve are able to proliferate to produce new nerve tissue. Co‐ordinating the regeneration of this tissue are Schwann cells (SCs), the main glial cells of the peripheral nervous system. SCs exist in architecturally stable structures that can persist for the lifetime of an animal, however, they are not postmitotic, in that following injury they are reprogrammed at high efficiency to a progenitor‐like state, with these cells acting to orchestrate the nerve regeneration process. During nerve regeneration, SCs show little plasticity, maintaining their identity in the repaired tissue. However, once free of the nerve environment they appear to exhibit increased plasticity with reported roles in the repair of other tissues. In this review, we will discuss the mechanisms underlying the homeostasis and regeneration of peripheral nerves and how reprogrammed progenitor‐like SCs have broader roles in the repair of other tissues with implications for pathologies such as cancer.

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Section: Scs As Promoters Of Tissue Regenerationmentioning

confidence: 99%

Schwann cell plasticity‐roles in tissue homeostasis, regeneration, and disease

Stierli

Imperatore

Lloyd

2019

Glia

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“…Perineural niche forms a specific background for cancer cells providing a favorable microenvironment for their survival and development. Cancer cells in perineural space are metabolically active with a higher proliferation ability and reduced apoptosis [18,73].…”

Section: Pni In Pcmentioning

confidence: 99%

“…The analysis performed on mice xenografts injected with PC-3 human PC cell line revealed that both tumor-infiltrating sympathetic fibers and intratumoral parasympathetic fibers arise from normal prostate tissue [30]. Moreover, sympathetic stimulation via β2adrenergic receptors seems to have a great impact on an-Pathobiology 2020;87:87-99 DOI: 10.1159/000505437 giogenesis, which in part explains anticancer activity of beta-blockers [18].…”

Section: Axonal Network In Tme and Nerve Fiber Density In Pcmentioning

confidence: 99%

“…Neural cancer microenvironment presents itself as a promising future target area for anti-cancer therapy. There are some potential molecular strategies for personalized treatment related to axonogenesis and neuronogenesis [18,52]. Anti-neurogenic therapies have already been tested in neurological disorders and there is feasibility of inhibiting NGF/proNGF as a therapeutic approach for PC [19].…”

Section: Neural Tme As a Potential Therapeutic Targetmentioning

confidence: 99%

“…During wound healing, nerves sprouting from preexisting nerve fibers form a neural network within the microenvironment [16]. The neural tissue elements, such as axons and neurons of different types, are important components of TME creating specific intra/ peritumoral neural milieu [17][18][19][20]. The knowledge on neural component of TME function and significance is still low but neurobiology of cancer has become a new discipline in oncology.…”

Section: Introductionmentioning

confidence: 99%

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Complexity of Neural Component of Tumor Microenvironment in Prostate Cancer

et al. 2020

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The tumor microenvironment (TME) plays an essential role in the development and progression of neoplasms. TME consists of the extracellular matrix and numerous specialized cells interacting with cancer cells by paracrine and autocrine mechanisms. Tumor axonogenesis and neoneurogenesis constitute a developing area of investigation. Prostate cancer (PC) is one of the most common malignancies in men worldwide. During the past years, more and more studies have shown that mechanisms leading to the development of PC are not confined only to the epithelial cancer cell, but also involve the tumor stroma. Different nerve types and neurotransmitters present within the TME are thought to be important factors in PC biology. Moreover, perineural invasion, which is a common way of PC spreading, in parallel creates the neural niche for malignant cells. Cancer neurobiology seems to have become a new discipline to explore the contribution of neoplastic cell interactions with the nervous system and the neural TME component, also to search for potential therapeutic targets in malignant tumors such as PC.

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Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer

Han

Jiang

et al. 2020

Molecular Oncology

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The adrenergic system contributes to the stress-induced onset and progression of cancer. Adrenergic fibers are the primary source of norepinephrine (NE). The underlying mechanisms involved in NE-induced colon cancer remain to be understood. In this study, we describe the function and regulatory network of NE in the progression of colon cancer. We demonstrate that NE-induced phosphorylation of cAMP response element-binding protein 1 (CREB1) promotes proliferation, migration, and invasion of human colon cancer cells. The downstream effector of NE, CREB1, bound to the promoter of miR-373 and transcriptionally activated its expression. miR-373 expression was shown to be necessary for NE-induced cell proliferation, invasion, and tumor growth. We confirmed that proliferation and invasion of colon cancer cells are regulated in vitro and in vivo by miR-373 through targeting of the tumor suppressors TIMP2 and APC. Our data suggest that NE promotes colon cancer cell proliferation and metastasis by activating the CREB1-miR-373 axis. The study of this novel signaling axis may provide mechanistic insights into the neural regulation of colon cancer and help in the design of future clinical studies on stress biology in colorectal cancer.Abbreviations APC, adenomatous polyposis coli; CRC, colorectal cancer; CREB1, cAMP response element-binding protein 1; NE, norepinephrine; qRT-PCR, quantitative real-time polymerase chain reaction; TCGA, The Cancer Genome Atlas; TH, tyrosine hydroxylase; TIMP2, tissue inhibitor of metalloproteinases 2.

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Tumor Neurobiology and the War of Nerves in Cancer

Cited by 181 publications

References 81 publications

Schwann cell plasticity‐roles in tissue homeostasis, regeneration, and disease

Schwann cell plasticity‐roles in tissue homeostasis, regeneration, and disease

Complexity of Neural Component of Tumor Microenvironment in Prostate Cancer

Norepinephrine‐CREB1‐miR‐373 axis promotes progression of colon cancer

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