The Autonomic Regulation of Tumor Growth and the Missing Links

Bautista, Maricris; Krishnan, Anand

doi:10.3389/fonc.2020.00744

Cited by 15 publications

(17 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In some of them tumor growth is promoted by adrenergic transmission. Conversely, cholinergic ones have stimulating or inhibitory properties or function depending on the type and stage of cancer ( 39 , 40 ). Neural stimulation was found to modify immune response, angiogenesis, apoptosis, cancer cell metabolism, and invasiveness ( 3 , 16 , 39 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, cholinergic ones have stimulating or inhibitory properties or function depending on the type and stage of cancer ( 39 , 40 ). Neural stimulation was found to modify immune response, angiogenesis, apoptosis, cancer cell metabolism, and invasiveness ( 3 , 16 , 39 , 41 ). Neurogenesis and axonogenesis may be considered as new hallmarks of cancer, similarly to the neuro-glial activation or angiogenesis ( 42 , 43 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

et al. 2021

View full text Add to dashboard Cite

BackgroundCancer stroma contains the neural compartment with specific components and action. Neural microenvironment processing includes among others axonogenesis, perineural invasion (PNI), neurosignaling, and tumor cell neural/neuroendocrine differentiation. Growing data suggest that tumor-neural crosstalk plays an important function in prostate cancer (PCa) biology. However, the mechanisms involved in PNI and axonogenesis, as well as their patho-clinical correlations in this tumor are unclear.MethodsThe present study was carried out on FFPE samples of 73 PCa and 15 benign prostate (BP) cases. Immunohistochemistry with neural markers PGP9.5, TH, and NFP was performed on constructed TMAs and selected tissue sections. The analyzed parameters of tumor innervation included small nerve density (ND) measured on pan-neural marker (PGP9.5) and TH s4tained slides, as well assessment of PNI presence and morphology. The qualitative and topographic aspects were studied. In addition, the expression of neuroendocrine marker chromogranin and NPY was assessed with dedicated indexes. The correlations of the above parameters with basic patho-clinical data such as patients’ age, tumor stage, grade, angioinvasion, and ERG status were examined.ResultsThe study showed that innervation parameters differed between cancer and BP. The neural network in PCa revealed heterogeneity, and ND PGP9.5 in tumor was significantly lower than in its periphery. The density of sympathetic TH-positive fibers and its proportion to all fibers was lower in cancer than in the periphery and BP samples. Perineural invasion was confirmed in 76% of cases, usually multifocally, occurring more commonly in tumors with a higher grade. NPY expression in PCa cells was common with its intensity often rising towards PNI. ERG+ tumors showed higher ND, more frequent PNI, and a higher stage. Moreover, chromogranin-positive cells were more pronounced in PCa with higher NPY expression.ConclusionsThe analysis showed an irregular axonal network in prostate cancer with higher neural density (panneural and adrenergic) in the surroundings and the invasive front. ND and PNI interrelated with NPY expression, neuroendocrine differentiation, and ERG status. The above findings support new evidence for the presence of autocrine and paracrine interactions in prostate cancer neural microenvironment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

et al. 2021

View full text Add to dashboard Cite

show abstract

“…As in the homeostasis of the non-diseased prostate [8], and the tumorous prostate for many decades, nerves were only recognized as pain carriers. [9] However, peripheral nerves have shown to modulate tumour growth and spread, feeding both cancer cells and stroma in the tumour environment [10,11]. This nervous dependence of tumours received initial attention due to invasion perineural, in which cancer cells migrate and invade nerves [12].…”

Section: Developmentmentioning

confidence: 99%

“…Although the perineural invasion was recognized long before as a complex physical interaction between cancer cells and nerves, a growth-stimulating interaction between each other has been experimentally demonstrated in the past two decades between cancer cells and neurons. Molecular signals derived from the tumour guide nerve infiltration into the tumour environment, while nerves that infiltrate the tumour provide molecular support to promote tumour growth and spread [9]. migration of prostate cancer cells were mutually beneficial when grown together.…”

Section: Developmentmentioning

confidence: 99%

Botulinum Toxin: The Promising Future of Prostate Cancer Treatment

Morales¹

2021

Archives of Cancer Biology and Therapy

View full text Add to dashboard Cite

Peripheral nerves have been shown to modulate the growth and spread of tumours in the prostate, feeding both cancer cells and the stroma in the tumour environment. Several in vitro and in vivo studies have reported the effect of botulinum toxin (BT) on tumour tissue in the prostate. BT in humans has been observed to cause increased apoptosis of cancer cells, with morphological changes characterized by extensive degenerative and atrophic areas of cancer, reduced cytoplasm, and pyknotic nuclei, compared to the characteristics of cancer tissues injected with saline solution. Based on this set of physiological and pathogenic knowledge, experimental, epidemiological, and clinical evidences have been generated that demonstrates the effect of BT on the control of prostate cancer, which represents a powerful therapeutic tool that would reduce mortality from prostate cancer.

show abstract

“…More recent data reveals that tumor growth itself may be driven by neurogenesis, or the recruitment of nerves by tumors as they grow. It has been shown that tumor-infiltrating nerve-derived molecules support tumor growth and dissemination [ 59 ]. Since the SNS can be continuously activated by chronic stress [ 60 ], the close proximity of these nerve endings to the tumor microenvironment raises considerable concern about the direct effects of secreted catecholamines within tumors [ 61 ].…”

Section: Modulation Of the Tumor Microenvironment By Chronic Stresmentioning

confidence: 99%

Highlighting the Potential for Chronic Stress to Minimize Therapeutic Responses to Radiotherapy through Increased Immunosuppression and Radiation Resistance

Chen

Singh

2020

Cancers

View full text Add to dashboard Cite

Ionizing radiation has been used in the treatment of cancer for more than 100 years. While often very effective, there is still a great effort in place to improve the efficacy of radiation therapy for controlling the progression and recurrence of tumors. Recent research has revealed the close interaction between nerves and tumor progression, especially nerves of the autonomic nervous system that are activated by a variety of stressful stimuli including anxiety, pain, sleep loss or depression, each of which is likely to be increased in cancer patients. A growing literature now points to a negative effect of chronic stressful stimuli in tumor progression. In this review article, we present data on the potential for adrenergic stress to influence the efficacy of radiation and in particular, its potential to influence the anti-tumor immune response, and the frequency of an “abscopal effect” or the shrinkage of tumors which are outside an irradiated field. We conclude that chronic stress can be a major impediment to more effective radiation therapy through mechanisms involving immunosuppression and increased resistance to radiation-induced tumor cell death. Overall, these data highlight the potential value of stress reduction strategies to improve the outcome of radiation therapy. At the same time, objective biomarkers that can accurately and objectively reflect the degree of stress in patients over prolonged periods of time, and whether it is influencing immunosuppression and radiation resistance, are also critically needed.

show abstract

The Autonomic Regulation of Tumor Growth and the Missing Links

Cited by 15 publications

References 63 publications

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

Botulinum Toxin: The Promising Future of Prostate Cancer Treatment

Highlighting the Potential for Chronic Stress to Minimize Therapeutic Responses to Radiotherapy through Increased Immunosuppression and Radiation Resistance

Contact Info

Product

Resources

About