Sensory nerves in the spotlight of the stem cell niche

Picoli, Caroline C.; Costa, Alinne C.; Rocha, Beatriz G S; Silva, Walison N.; Santos, Gabryella S P; Prazeres, Pedro H. D. M.; Costa, P.A.C.R.; Oropeza, Anderson; Silva, Rodrigo A. da; Azevedo, Vasco; Resende, Rodrigo R.; Cunha, Thiago Mattar; Mintz, Akiva; Birbrair, Alexander

doi:10.1002/sctm.20-0284

Cited by 13 publications

(5 citation statements)

References 168 publications

(312 reference statements)

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“…During the past decade, surgical, pharma cological and genetic denervation models have established the nervous system's role in regulating the HSC niche 8 . But these studies mainly focused on sympathetic nerve fibres (those involved in involuntary actions of the body), showing that they help to maintain the functional integrity of the niche 9 . Here, Gao et al have found that the adhesion of HSCs to their bonemarrow niche and their ability to mobilize to the peripheral blood is controlled by nociceptive neurons acting directly on HSCs through secretion of the neurotransmitter CGRP.…”

mentioning

confidence: 99%

Pain-sensing neurons mobilize blood stem cells from bone marrow

Tikhonova¹,

Aifantis²

2020

Nature

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mentioning

confidence: 99%

Pain-sensing neurons mobilize blood stem cells from bone marrow

Tikhonova¹,

Aifantis²

2020

Nature

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“…For instance, it has been documented that the same drug that is used to denervate sensory neurons, resiniferatoxin (RTX), an analogue of capsaicin, also induces stress by causing hyperactivation of the sympathetic nervous system [ 16 , 62 , 157 ]. These studies also revealed that sensory nerves may tune down sympathetic nerve activity [ 16 , 62 , 105 ]. Sympathetic neurons release norepinephrine [ 70 , 123 ], which has been shown to strongly induce tumorigenesis [ 1 , 60 , 154 ].…”

Section: Discussionmentioning

confidence: 99%

Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

Costa

Silva

Prazeres

et al. 2021

acta neuropathol commun

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Sensory neurons have recently emerged as components of the tumor microenvironment. Nevertheless, whether sensory neuronal activity is important for tumor progression remains unknown. Here we used Designer Receptors Exclusively Activated by a Designer Drug (DREADD) technology to inhibit or activate sensory neurons’ firing within the melanoma tumor. Melanoma growth and angiogenesis were accelerated following inhibition of sensory neurons’ activity and were reduced following overstimulation of these neurons. Sensory neuron-specific overactivation also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of melanoma biopsies revealed that increased expression of sensory neurons-related genes within melanoma was associated with improved survival. These findings suggest that sensory innervations regulate melanoma progression, indicating that manipulation of sensory neurons’ activity may provide a valuable tool to improve melanoma patients’ outcomes.

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“…This results in the excessive activation of sympathetic neurons, leading to the dysfunction of multiple organs (184,185). Finally, activation of PSNs can also attenuate sympathetic tone, as demonstrated in the bone marrow to regulate bone metabolism (186)(187)(188).…”

Section: Cancer Pain and Psychological Stressmentioning

confidence: 99%

From pain to tumor immunity: influence of peripheral sensory neurons in cancer

Mardelle,

Bretaud,

Daher

et al. 2024

Front. Immunol.

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The nervous and immune systems are the primary sensory interfaces of the body, allowing it to recognize, process, and respond to various stimuli from both the external and internal environment. These systems work in concert through various mechanisms of neuro-immune crosstalk to detect threats, provide defense against pathogens, and maintain or restore homeostasis, but can also contribute to the development of diseases. Among peripheral sensory neurons (PSNs), nociceptive PSNs are of particular interest. They possess a remarkable capability to detect noxious stimuli in the periphery and transmit this information to the brain, resulting in the perception of pain and the activation of adaptive responses. Pain is an early symptom of cancer, often leading to its diagnosis, but it is also a major source of distress for patients as the disease progresses. In this review, we aim to provide an overview of the mechanisms within tumors that are likely to induce cancer pain, exploring a range of factors from etiological elements to cellular and molecular mediators. In addition to transmitting sensory information to the central nervous system, PSNs are also capable, when activated, to produce and release neuropeptides (e.g., CGRP and SP) from their peripheral terminals. These neuropeptides have been shown to modulate immunity in cases of inflammation, infection, and cancer. PSNs, often found within solid tumors, are likely to play a significant role in the tumor microenvironment, potentially influencing both tumor growth and anti-tumor immune responses. In this review, we discuss the current state of knowledge about the degree of sensory innervation in tumors. We also seek to understand whether and how PSNs may influence the tumor growth and associated anti-tumor immunity in different mouse models of cancer. Finally, we discuss the extent to which the tumor is able to influence the development and functions of the PSNs that innervate it.

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Sensory nerves in the spotlight of the stem cell niche

Cited by 13 publications

References 168 publications

Pain-sensing neurons mobilize blood stem cells from bone marrow

Pain-sensing neurons mobilize blood stem cells from bone marrow

Chemogenetic modulation of sensory neurons reveals their regulating role in melanoma progression

From pain to tumor immunity: influence of peripheral sensory neurons in cancer

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