Breast cancer induced nociceptor aberrant growth and collateral sensory axonal branching

Austin, Matt; Elliott, Laura; Nicolaou, Niovi; Grabowska, Anna; Hulse, Richard P.

doi:10.18632/oncotarget.20609

Cited by 26 publications

(29 citation statements)

References 51 publications

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“…In support of such a function, oesophageal, colorectal cancer [45], breast cancer [243] and cardiac carcinoma [244] were also found to promote neuritogenesis in vitro. More precisely, it was determined that VEGFa released by breast cancer carcinoma [245] drives neuritogenesis, whilst neuropeptides released by sensory neurons enhance chemokinesis [243]. Besides VEGFa, cancer cells released NGF and neurturin can also trigger neurite outgrowth.…”

Section: Cancermentioning

confidence: 99%

Profiling of how nociceptor neurons detect danger – new and old foes

et al. 2019

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The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro‐immune interplay is still ill‐defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH1‐mediated immunity but also as drivers of TH2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide‐ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

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Section: Cancermentioning

confidence: 99%

Profiling of how nociceptor neurons detect danger – new and old foes

et al. 2019

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“…Tumour innervation has been established in several other malignancies 25 . For example, adrenergic innervation is demonstrated in breast cancer, where nerves infiltrate the tumour microenvironment and are associated with lymph node invasion 10,26 . In prostate cancer, both adrenergic and cholinergic nerves are present, and nerve density is increased inside and around prostate cancer compared to benign prostate, and correlates with more aggressive tumours 2,27,28 .…”

Section: Discussionmentioning

confidence: 99%

Innervation of papillary thyroid cancer and its association with extra-thyroidal invasion

Rowe

Dill

Griffin

et al. 2020

Sci Rep

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Nerves are emerging regulators of cancer progression and in several malignancies innervation of the tumour microenvironment is associated with tumour aggressiveness. However, the innervation of thyroid cancer is unclear. Here, we investigated the presence of nerves in thyroid cancers and the potential associations with clinicopathological parameters. Nerves were detected by immunohistochemistry using the pan-neuronal marker PGP9.5 in whole-slide sections of papillary thyroid cancer (ptc) (n = 75), compared to follicular thyroid cancer (FTC) (n = 13), and benign thyroid tissues (n = 26). Nerves were detected in most normal thyroid tissues and thyroid cancers, but nerve density was increased in PTC (12 nerves/cm 2 [IQR 7-21]) compared to benign thyroid (6 nerves/cm 2 [IQR: 3-10]) (p = 0.001). In contrast, no increase in nerve density was observed in FTC. In multivariate analysis, nerve density correlated positively with extrathyroidal invasion (p < 0.001), and inversely with tumour size (p < 0.001). The majority of nerves were adrenergic, although cholinergic and peptidergic innervation was detected. Perineural invasion was present in 35% of PTC, and was independently associated with extrathyroidal invasion (p = 0.008). This is the first report of infiltration of nerves into the tumour microenvironment of thyroid cancer and its association with tumour aggressiveness. The role of nerves in thyroid cancer pathogenesis should be further investigated.

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“…The molecules secreted by tumor cells contribute to develop their own microenvironment, modifying the extracellular matrix that surrounds them and the number of sensory neurons and modulating the immune system surveillance. 3 , 4 These events protect the tumors of immune regulatory signals, favoring their growth and invasion, 3 rendering the factors involved in these chronic inflammatory processes potential therapeutic targets for cancer.…”

Section: Introductionmentioning

confidence: 99%

“…This special pattern of response of the channel to increasing doses of capsaicin may be very relevant in the context of advanced breast cancer tumors, where the overexpressing TRPV1 sensory neurons exhibit aberrant collateral axonal branching. 4 The utilization of capsaicin in this context could reduce the aberrant activity of sensory neurons by blocking the tumor growth and, concomitantly, the pain sensation. 4 , 10 Finding the minimum concentration necessary to induce cell death without causing excessive pain or inflammation can thus be considered as an important constraint to assess treatment efficacy of TRPV1 activators.…”

Section: Introductionmentioning

confidence: 99%

“… 4 The utilization of capsaicin in this context could reduce the aberrant activity of sensory neurons by blocking the tumor growth and, concomitantly, the pain sensation. 4 , 10 Finding the minimum concentration necessary to induce cell death without causing excessive pain or inflammation can thus be considered as an important constraint to assess treatment efficacy of TRPV1 activators. 10 …”

Section: Introductionmentioning

confidence: 99%

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Intracellular aggregated TRPV1 is associated with lower survival in breast cancer patients

Lozano¹,

Córdova²,

Marchant³

et al. 2018

BCTT

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BackgroundBreast cancer is a malignant disease that represents an important public health burden. The description of new molecular markers can be important to diagnosis, classification, and treatment. Transient receptor potential vanilloid 1 (TRPV1) polymodal channel is expressed in different neoplastic tissues and cell lines of breast cancer and associated with the regulation of tumor growth, tumor neurogenesis, cancer pain, and malignant progression of cancer. In primary and metastatic breast cancer tumors, TRPV1 is expressed during neoplastic transformation, invasive behavior, and resistance to cytotoxic therapy.ObjectiveThe objective of this study was to describe the subcellular distribution of TRPV1 in invasive breast carcinomas and its association with survival.MethodsIn 33 cases of invasive breast carcinomas, we identified immunohistochemical and immunofluorescent expression patterns of TRPV1 compared to healthy breast tissue. We characterized the expression of TRPV1 induced by estrogens in breast cancer cell lines MCF-7 and MDA to establish a model of the TRPV1–estrogen relationship regarding the malignant potential. We examined the association of TRPV1 patterns with patients’ survival with the Kaplan–Meyer model, using the log-rank test at 5 years of follow-up. The relation of TRPV1 expression patterns to the St. Gallen breast cancer subtypes was also tested.ResultsBased on immunohistochemical expression pattern of TRPV1, we distinguished two main categories of breast cancer tissue, a “classical category” that exhibited diffuse expression of the channel and a “non-classical category” that expressed the channel in aggregates at the ER/Golgi and/or surrounding these structures. The classical pattern of TRPV1 was associated with a higher survival rate. In breast cancer cell lines, increasing doses of estrogens induced increased TRPV1 expression with nonclassical patterns at higher doses via a mechanism dependent on ER α.ConclusionThe expression and distribution of TRPV1 in invasive breast carcinomas may be considered as a biomarker for prognosis of the disease and a probable therapeutic target.

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Breast cancer induced nociceptor aberrant growth and collateral sensory axonal branching

Cited by 26 publications

References 51 publications

Profiling of how nociceptor neurons detect danger – new and old foes

Profiling of how nociceptor neurons detect danger – new and old foes

Innervation of papillary thyroid cancer and its association with extra-thyroidal invasion

Intracellular aggregated TRPV1 is associated with lower survival in breast cancer patients

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