Tumour innervation and neurosignalling in prostate cancer

March, Brayden; Faulkner, Sam; Jobling, Phillip; Steigler, Allison; Blatt, Alison; Denham, J.W.; Hondermarck, Hubert

doi:10.1038/s41585-019-0274-3

Cited by 61 publications

(55 citation statements)

References 134 publications

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“…6 Recent evidence from animal models has demonstrated the importance of the role of nerve-cancer cell crosstalk in prostate cancer. 27 In the mouse, denervation of autonomic nerves prevents prostate cancer growth and dissemination, and although the mechanism has yet to be fully elucidated, this involves the stimulation of beta-adrenergic and muscarinic receptors in both cancer and stromal cells contributing to the stimulation of prostate cancer growth and metastasis. 28,29 PNI results from a bi-directional interaction between nerves and cancer cells and the presence of PNI may indicate active nerve-cancer cell crosstalk, which could promote tumour aggressiveness.…”

Section: Discussionmentioning

confidence: 99%

Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial

et al. 2020

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Aims Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10 years outcome data from the TROG 03.04 RADAR trial. Methods Diagnostic prostate biopsies from 976 patients were reviewed and the presence of PNI noted. Patients were followed for 10 years according to the trial protocol or until death. The primary endpoint for the study was time to bone metastasis. Secondary endpoints included time to soft tissue metastasis, transition to castration resistance, prostate cancer‐specific mortality and all‐cause mortality. Results PNI was detected in 449 cases (46%), with 234 cases (24%) having PNI in more than one core. The presence of PNI was significantly associated with higher ISUP grade, clinical T staging category, National Comprehensive Cancer Network risk group, and percent positive biopsy cores. The cumulative probability of bone metastases according to PNI status was significant over the 10 years follow‐up interval of the study (log‐rank test P < 0.0001). PNI was associated with all endpoints on univariable analysis. After adjusting for baseline clinicopathological and treatment factors, bone metastasis was the only endpoint in which PNI retained its prognostic significance (hazard ratio 1.42, 95% confidence interval 1.05–1.92, P = 0.021). Conclusions The association between PNI and the development of bone metastases supports the inclusion of this parameter as a component of the routine histology report. Further this association suggests that evaluation of PNI may assist in selecting those patients who should be monitored more closely during follow‐up.

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Section: Discussionmentioning

confidence: 99%

Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial

et al. 2020

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“…Regarding the nervous system in the context of cancer progression, recent reports support the idea that nervous cells and soluble factors inherent to their communication also contribute to cancer progression. 6 Therefore, translational research focuses on disrupting cellular communication as a strategy to fight tumor growth and dissemination. In the next sections, we discuss how tumor cells communicate with the immune (Section "Evasion of the immune response: aberrant communication between cancer and immune cells") and nervous system (Sections "Reciprocal communication between cancer cells and the nervous system promotes tumor progression" and "Classical central nervous system neurotransmitters (dopamine, glutamate, and GABA) impact cancer progression").…”

Section: Cell Communication Network In Cancermentioning

confidence: 99%

“…3 insert). 6,190 Another putative mechanism is linked to the immunomodulatory role of autonomic mediators which decrease antitumor immune responses. Neuropathic pain suffered by cancer patients is exacerbated by the aberrant communication between autonomic and sensorial fibers; antidromic spontaneous shots of sensorial fibers can enrich the TME.…”

Section: Sema4f Knock Downmentioning

confidence: 99%

“…3 In patients, the immune and nervous systems are commonly coopted by tumors to favor cancer progression. [4][5][6] At metastatic stage, the deadliest phase of cancer progression, cancer cells access the systemic circulation, move and implant in distant organs where favorable substrates allow cancer cell colonization and expansion. 7 In the process, reciprocal communication between immune and nervous systems correlates with bad prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Cervantes‐Villagrana

Albores-García

Cervantes-Villagrana

et al. 2020

Sig Transduct Target Ther

147

112

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Normal cells are hijacked by cancer cells forming together heterogeneous tumor masses immersed in aberrant communication circuits that facilitate tumor growth and dissemination. Besides the well characterized angiogenic effect of some tumor-derived factors; others, such as BDNF, recruit peripheral nerves and leukocytes. The neurogenic switch, activated by tumor-derived neurotrophins and extracellular vesicles, attracts adjacent peripheral fibers (autonomic/sensorial) and neural progenitor cells. Strikingly, tumor-associated nerve fibers can guide cancer cell dissemination. Moreover, IL-1β, CCL2, PGE 2 , among other chemotactic factors, attract natural immunosuppressive cells, including T regulatory (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, to the tumor microenvironment. These leukocytes further exacerbate the aberrant communication circuit releasing factors with neurogenic effect. Furthermore, cancer cells directly evade immune surveillance and the antitumoral actions of natural killer cells by activating immunosuppressive mechanisms elicited by heterophilic complexes, joining cancer and immune cells, formed by PD-L1/PD1 and CD80/CTLA-4 plasma membrane proteins. Altogether, nervous and immune cells, together with fibroblasts, endothelial, and bone-marrow-derived cells, promote tumor growth and enhance the metastatic properties of cancer cells. Inspired by the demonstrated, but restricted, power of anti-angiogenic and immune cell-based therapies, preclinical studies are focusing on strategies aimed to inhibit tumor-induced neurogenesis. Here we discuss the potential of anti-neurogenesis and, considering the interplay between nervous and immune systems, we also focus on anti-immunosuppression-based therapies. Small molecules, antibodies and immune cells are being considered as therapeutic agents, aimed to prevent cancer cell communication with neurons and leukocytes, targeting chemotactic and neurotransmitter signaling pathways linked to perineural invasion and metastasis.

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“…Lymphovascular invasion (LVI) and perineural invasion (PNI) are independent predictors of poorer prognosis in prostate adenocarcinoma [18]. Initially, they were considered as possible spread paths for cancer cells [19] but recent investigations in animal models show now more complex molecular processes in PNI [20].…”

Section: Discussionmentioning

confidence: 99%

MRI detected extaprostatic extension (EPE) in prostate cancer: Do all T3a patients have the same outcomes?

Gómez-Iturriaga

Büchser

Miguel

et al. 2020

Clinical and Translational Radiation Oncology

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Tumour innervation and neurosignalling in prostate cancer

Cited by 61 publications

References 134 publications

Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial

Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

MRI detected extaprostatic extension (EPE) in prostate cancer: Do all T3a patients have the same outcomes?

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