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Article ; Online: Neural regulation of body polarities in nereid worm regeneration

Benoni Boilly / Hubert Hondermarck / Yolande Boilly‐Marer

FASEB BioAdvances, Vol 4, Iss 1, Pp 22-

2022 Volume 28

Abstract: Abstract Nerve dependence in regeneration has been established more than 200 years ago but the mechanisms by which nerves are necessary to regeneration remain to be fully elucidated. Aside from their direct impact in stimulating cellular growth, nerves ... ...

Abstract	Abstract Nerve dependence in regeneration has been established more than 200 years ago but the mechanisms by which nerves are necessary to regeneration remain to be fully elucidated. Aside from their direct impact in stimulating cellular growth, nerves also have a role on the establishment of body polarities (antero‐posterior and dorso‐ventral patterns) and this has been particularly well studied in nereid annelid worms. Nereids can regenerate appendages (parapodia) and the tail (body segments). In both parapodia and tail regeneration, the presence of the nerve cord is necessary to the establishment of body polarities. In this review, we will detail the experimental procedures which have been conducted in nereids to elucidate the role of the nerve cord in the establishment of the antero‐posterior and dorso‐ventral polarities. Most of the studies reported here were published several decades ago and based on anatomical and histological analyses; this review should constitute a knowledgebase and an inspiration for needed modern‐time explorations at the molecular levels to elucidate the impact of the nervous system in the acquisition of body polarities.
Keywords	annelids ; body polarity ; nerve ; positional information ; regeneration ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The nervous system

Hubert Hondermarck / Pearl S. Huang / John A. Wagner

FASEB BioAdvances, Vol 3, Iss 11, Pp 944-

Orchestra conductor in cancer, regeneration, inflammation and immunity

2021 Volume 952

Abstract: Abstract Although the role of nerves in stimulating cellular growth and dissemination has long been described in tissue regeneration studies, until recently a similar trophic role of nerves in disease was not well recognized. However, recent studies in ... ...

Abstract	Abstract Although the role of nerves in stimulating cellular growth and dissemination has long been described in tissue regeneration studies, until recently a similar trophic role of nerves in disease was not well recognized. However, recent studies in oncology have demonstrated that the growth and dissemination of cancers also requires the infiltration of nerves in the tumor microenvironment. Nerves generate various neurosignaling pathways, which orchestrate cancer initiation, progression, and metastases. Similarly, nerves are increasingly implicated for their regulatory functions in immunity and inflammation. This orchestrator role of nerves in cellular and molecular interactions during regeneration, cancer, immunity, and inflammation offers new possibilities for targeting or enhancing neurosignaling in human health and diseases.
Keywords	cancer ; immunity ; inflammation ; nerves ; nervous system ; regeneration ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The role of growth factor receptors in viral infections

Hubert Hondermarck / Nathan W. Bartlett / Victor Nurcombe

FASEB BioAdvances, Vol 2, Iss 5, Pp 296-

An opportunity for drug repurposing against emerging viral diseases such as COVID‐19?

2020 Volume 303

Abstract: Abstract Growth factor receptors are known to be involved in the process of viral infection. Many viruses not only use growth factor receptors to physically attach to the cell surface and internalize, but also divert receptor tyrosine kinase signaling in ...

Abstract	Abstract Growth factor receptors are known to be involved in the process of viral infection. Many viruses not only use growth factor receptors to physically attach to the cell surface and internalize, but also divert receptor tyrosine kinase signaling in order to replicate. Thus, repurposing drugs that have initially been developed to target growth factor receptors and their signaling in cancer may prove to be a fast track to effective therapies against emerging new viral infections, including the coronavirus disease 19 (COVID‐19).
Keywords	cancer drugs ; COVID‐19 ; growth factors ; heparan sulfate ; heparin ; inhibitors ; Biology (General) ; QH301-705.5 ; covid19
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ELISA‐based quantification of neurotrophic growth factors in urine from prostate cancer patients

Brayden March / Kathleen Rebecca Lockhart / Sam Faulkner / Markus Smolny / Robert Rush / Hubert Hondermarck

FASEB BioAdvances, Vol 3, Iss 11, Pp 888-

2021 Volume 896

Abstract: Abstract Non‐invasive procedures are needed for prostate cancer management, and urine represents a potential source of new biomarkers with translational value. Recent evidence has shown that the growth of new nerves in the tumor microenvironment is ... ...

Abstract	Abstract Non‐invasive procedures are needed for prostate cancer management, and urine represents a potential source of new biomarkers with translational value. Recent evidence has shown that the growth of new nerves in the tumor microenvironment is essential to prostate cancer progression. Neurotrophic growth factors are expressed by prostate cancer cells and contribute to prostate tumor innervation, but their presence in urine is unclear. In the present study, we have assayed the concentration of neurotrophic factors in the urine of prostate cancer patients. Urine was collected from a prospective cohort of 45 men with prostate cancer versus 30 men without cancer and enzyme‐linked immunosorbent assay was used to quantify nerve growth factor (NGF) and its precursor proNGF, brain‐derived neurotrophic factor (BDNF) and proBDNF, neurotrophin‐3, neurotrophin‐4/5, and glia‐derived neurotrophic growth factor. The results show that neurotrophic factors are detectable in various concentrations in both cancer and healthy urine, but no significant difference was found. Also, no association was observed between neurotrophic factor concentrations and prostate cancer grade. This study is the first quantification of neurotrophins in urine, and although no significant differences were observed between prostate cancer patients versus those without prostate cancer, or between prostate cancers of various grades, the potential value of neurotrophins for prostate cancer diagnosis and prognosis warrants further investigations in larger patient cohorts.
Keywords	biomarkers ; diagnosis ; neurotrophic growth factors ; prognosis ; prostate cancer ; urine ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Expression of NGF/proNGF and Their Receptors TrkA, p75 NTR and Sortilin in Melanoma

Mark Marsland / Amiee Dowdell / Chen Chen Jiang / James S. Wilmott / Richard A. Scolyer / Xu Dong Zhang / Hubert Hondermarck / Sam Faulkner

International Journal of Molecular Sciences, Vol 23, Iss 4260, p

2022 Volume 4260

Abstract: There is increasing evidence that nerve growth factor (NGF) and its receptors, the neurotrophic receptor tyrosine kinase 1 (NTRK1/TrkA), the common neurotrophin receptor (NGFR/p75 NTR ) and the membrane receptor sortilin, participate in cancer growth. In ...

Abstract	There is increasing evidence that nerve growth factor (NGF) and its receptors, the neurotrophic receptor tyrosine kinase 1 (NTRK1/TrkA), the common neurotrophin receptor (NGFR/p75 NTR ) and the membrane receptor sortilin, participate in cancer growth. In melanoma, there have been some reports suggesting that NGF, TrkA and p75 NTR are dysregulated, but the expression of the NGF precursor (proNGF) and its membrane receptor sortilin is unknown. In this study, we investigated the expression of NGF, proNGF, TrkA, p75 NTR and sortilin by immunohistochemistry in a series of human tissue samples ( n = 100), including non-cancerous nevi ( n = 20), primary melanomas ( n = 40), lymph node metastases ( n = 20) and distant metastases ( n = 20). Immunostaining was digitally quantified and revealed NGF and proNGF were expressed in all nevi and primary melanomas, and that the level of expression decreased from primary tumors to melanoma metastases ( p = 0.0179 and p < 0.0001, respectively). Interestingly, TrkA protein expression was high in nevi and thin primary tumors but was strongly downregulated in thick primary tumors ( p < 0.0001) and metastases ( p < 0.0001). While p75 NTR and sortilin were both expressed in most nevi and melanomas, there was no significant difference in expression between them. Together, these results pointed to a downregulation of NGF/ProNGF and TrkA in melanoma, and thus did not provide evidence to support the use of anti-proNGF/NGF or anti-TrkA therapies in advanced and metastatic forms of melanoma.
Keywords	melanoma ; NGF ; proNGF ; TrkA ; p75 NTR ; sortilin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	333
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Innervation of papillary thyroid cancer and its association with extra-thyroidal invasion

Christopher W. Rowe / Tony Dill / Nathan Griffin / Phil Jobling / Sam Faulkner / Jonathan W. Paul / Simon King / Roger Smith / Hubert Hondermarck

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 9

Abstract: Abstract 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 ... ...

Abstract	Abstract 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/cm2 [IQR 7–21]) compared to benign thyroid (6 nerves/cm2 [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.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nerve growth factor and its receptor tyrosine kinase TrkA are overexpressed in cervical squamous cell carcinoma

Sam Faulkner / Nathan Griffin / Christopher W. Rowe / Phillip Jobling / Janine M. Lombard / Sonia M. Oliveira / Marjorie M. Walker / Hubert Hondermarck

FASEB BioAdvances, Vol 2, Iss 7, Pp 398-

2020 Volume 408

Abstract: Abstract Nerve growth factor (NGF) and its receptors are increasingly implicated in cancer progression, but their expression in cervical cancer is unclear. The objective of this study was to define the protein expression of NGF, its precursor (proNGF), ... ...

Abstract	Abstract Nerve growth factor (NGF) and its receptors are increasingly implicated in cancer progression, but their expression in cervical cancer is unclear. The objective of this study was to define the protein expression of NGF, its precursor (proNGF), as well as their receptors, the tyrosine kinase receptor TrkA, the common neurotrophin receptor p75NTR and the pro‐neurotrophin receptor sortilin in cervical cancer. Immunohistochemistry was performed in a cohort of cervical cancers (n = 287), including the two major subtypes of the disease: squamous cell carcinomas (SCC) and adenocarcinomas (AC). Normal cervical tissues (n = 28) were also analyzed. Protein expression was determined by computer‐based digital quantification of staining intensity and comparative statistical analyses were made with clinicopathological parameters including histological subtype, age, grade, tumor size, lymph node invasion, and stage. The expression of NGF, proNGF, TrkA, p75NTR, and sortilin was higher in cervical cancer compared to normal cervical tissues. NGF and TrkA were found overexpressed in SCC compared to AC (P = .0006 and P < .0001, respectively). The expression of NGF (P = .0053), proNGF (P = .0022), and p75NTR (P = .0002), but not that of TrkA or sortilin, was associated with increasing grade in SCC. In addition, nerve infiltration into the tumor microenvironment was assessed using the pan‐neuronal marker PGP9.5. Infiltrating nerves were detected in 27% of cervical tumors and expressed TrkA. Functional investigations using the HELA cervical cancer cell line indicated that the Trk tyrosine kinase inhibitor GNF‐5837 reduced cell viability through decreased ERK1/2 activation. Together, these data reveal the overexpression of NGF and TrkA in cervical SCC, suggesting a potential therapeutic value of targeting the NGF‐TrkA signaling pathway in this subtype of cervical cancer.
Keywords	cervical cancer ; nerves ; NGF ; p75NTR ; proNGF ; sortilin ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Tumor innervation and clinical outcome in pancreatic cancer

Aysha Ferdoushi / Nathan Griffin / Mark Marsland / Xiaoyue Xu / Sam Faulkner / Fangfang Gao / Hui Liu / Simon J. King / James W. Denham / Dirk F. van Helden / Phillip Jobling / Chen Chen Jiang / Hubert Hondermarck

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 10

Abstract: Abstract Pancreatic cancer is a highly aggressive malignancy characterized by poor survival, recurrence after surgery and resistance to therapy. Nerves infiltrate the microenvironment of pancreatic cancers and contribute to tumor progression, however the ...

Abstract	Abstract Pancreatic cancer is a highly aggressive malignancy characterized by poor survival, recurrence after surgery and resistance to therapy. Nerves infiltrate the microenvironment of pancreatic cancers and contribute to tumor progression, however the clinicopathological significance of tumor innervation is unclear. In this study, the presence of nerves and their cross-sectional size were quantified by immunohistochemistry for the neuronal markers S-100, PGP9.5 and GAP-43 in a series of 99 pancreatic cancer cases versus 71 normal adjacent pancreatic tissues. A trend was observed between the presence of nerves in the tumor microenvironment of pancreatic cancer and worse overall patient survival (HR = 1.8, 95% CI 0.77–4.28, p = 0.08). The size of nerves, as measured by cross-sectional area, were significantly higher in pancreatic cancer than in the normal adjacent tissue (p = 0.002) and larger nerves were directly associated with worse patient survival (HR = 0.41, 95% CI 0.19–0.87, p = 0.04). In conclusion, this study suggests that the presence and size of nerves within the pancreatic cancer microenvironment are associated with tumor aggressiveness.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High nerve density in breast cancer is associated with poor patient outcome

Dong Li / Li Na Hu / Si Min Zheng / Ting La / Li Yuan Wei / Xiao Jun Zhang / Zhen Hua Zhang / Jun Xing / Li Wang / Ruo Qi Li / Qin Zhu / Rick F. Thorne / Yu Chen Feng / Hubert Hondermarck / Xu Dong Zhang / Li Li / Jin Nan Gao

FASEB BioAdvances, Vol 4, Iss 6, Pp 391-

2022 Volume 401

Abstract: Abstract Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~ ... ...

Abstract	Abstract Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to clarify the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features. Immunohistochemical staining was conducted in formalin‐fixed paraffin‐embedded breast cancer tissue sections using antibodies against the pan‐neuronal markers protein gene product 9.5 and growth‐associated protein 43, and the sympathetic nerve‐specific marker tyrosine hydroxylase. Nerve trunks and isolated nerve fibers were quantitated. The chi‐squared test was used to determine the associations between nerve counts and clinicopathological parameters. The log‐rank test was used to compare differences in patient progression‐free survival (PFS) and overall survival (OS). The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin. While high density of nerve trunks or isolated nerve fibers was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.
Keywords	breast cancer ; cancer neuroscience ; innervation ; nerves ; tumor microenvironment ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The neurotrophic tyrosine kinase receptor TrkA and its ligand NGF are increased in squamous cell carcinomas of the lung

Fangfang Gao / Nathan Griffin / Sam Faulkner / Christopher W. Rowe / Lily Williams / Severine Roselli / Rick F. Thorne / Aysha Ferdoushi / Phillip Jobling / Marjorie M. Walker / Hubert Hondermarck

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 11

Abstract: Abstract The neurotrophic tyrosine kinase receptor TrkA (NTRK1) and its ligand nerve growth factor (NGF) are emerging promoters of tumor progression. In lung cancer, drugs targeting TrkA are in clinical trials, but the clinicopathological significance of ...

Abstract	Abstract The neurotrophic tyrosine kinase receptor TrkA (NTRK1) and its ligand nerve growth factor (NGF) are emerging promoters of tumor progression. In lung cancer, drugs targeting TrkA are in clinical trials, but the clinicopathological significance of TrkA and NGF, as well as that of the precursor proNGF, the neurotrophin co-receptor p75NTR and the proneurotrophin co-receptor sortilin, remains unclear. In the present study, analysis of these proteins was conducted by immunohistochemistry and digital quantification in a series of 204 lung cancers of different histological subtypes versus 121 normal lung tissues. TrkA immunoreactivity was increased in squamous cell carcinoma compared with benign and other malignant lung cancer histological subtypes (p < 0.0001). NGF and proNGF were also increased in squamous cell carcinoma, as well as in adenocarcinoma (p < 0.0001). In contrast, p75NTR was increased across all lung cancer histological subtypes compared to normal lung (p < 0.0001). Sortilin was higher in adenocarcinoma and small cell carcinoma (p < 0.0001). Nerves in the tumor microenvironment were negative for TrkA, NGF, proNGF, p75NTR and sortilin. In conclusion, these data suggest a preferential therapeutic value of targeting the NGF-TrkA axis in squamous cell carcinomas of the lung.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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