Neural Invasion in Pancreatic Cancer: The Past, Present and Future

Demir, Ihsan Ekin; Ceyhan, Güralp O.; Liebl, Florian; D’Haese, Jan; Maak, Matthias; Friess, Helmut

doi:10.3390/cancers2031513

Cited by 92 publications

(99 citation statements)

References 45 publications

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“…Indeed, a direct consequence of this neural remodeling in PDA is the appearance of perineural invasion (PNI) events, marked by the cancer cell's capacity to invade pancreatic nerves present within the tumor (15,16). In PDA, PNI is considered as an indicator of an aggressive Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.…”

Section: Introductionmentioning

confidence: 99%

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

et al. 2018

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Abstract:Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive stroma and pathogenic modifications to the peripheral nervous system that elevate metastatic capacity. In this study, we show that the IL-6-related stem cell promoting factor LIF supports PDACassociated neural remodeling (PANR). LIF was overexpressed in tumor tissue compared to healthy pancreas, but its receptors LIFR and gp130 were expressed only in intratumoral Significance:This study suggests a target to limit neural remodeling in pancreatic cancer, which contributes to poorer quality of life and heightened metastatic progression in patients.

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Section: Introductionmentioning

confidence: 99%

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

et al. 2018

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“…PNI is the initial infiltration of tumor cells into the surrounding nerves and along the nerves, thus providing an alternative route for metastatic spread. It is considered the foremost reason for local tumor recurrence after curative resection and correlates with the abdominal pain sensation of pancreatic cancer patients (6,7). The molecular changes leading to PNI are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling

Guo

et al. 2013

Molecular Cancer Therapeutics

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Perineural invasion (PNI) is one of the most important causes of local recurrence and poor survival in pancreatic cancer. However, the exact mechanism of PNI is still not clear. In this study, we sought to identify the reciprocal signaling interactions between sympathetic nerves and pancreatic cancer cells and the underlying mechanisms. We used mouse dorsal root ganglia and pancreatic cancer cells cocultured in vitro, cellular and molecular biology, and animal models to evaluate the function of the sympathetic neurotransmitter norepinephrine (NE) in PNI progression and pathogenesis. NE promoted PNI of pancreatic cancer cells and increased levels of phosphorylated STAT3 in a concentration-dependent manner. NE-mediated activation of STAT3 was inhibited by blocking b-adrenergic receptors (AR) and by blocking protein kinase A, but not through blocking a-AR. Blocking STAT3 could inhibit NE-induced NGF, MMP2, and MMP9 expression and attenuate the migratory, invasive ability and PNI of pancreatic cancer cells. Furthermore, PNI of pancreatic cancer cells was blocked by treatment with a STAT3 phosphorylation inhibitor in vivo. These studies show that NE plays a critical role in pancreatic cancer PNI development and progression through the b-AR/PKA/STAT3 signaling pathway. Reciprocal signaling interactions between the sympathetic nerves and pancreatic cancer cells critically contribute to pancreatic cancer PNI pathogenesis. Inhibition of the activity of sympathetic nerves or STAT3 may be potential strategies for pancreatic cancer PNI therapy.

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“…Moreover, tumor cells improve the growth of nerve cells by secreting a number of cytokines, such as neurotrophic factors, chemokines, and nerve adhesion factors (1,17,21,22). It has been reported previously that some tumor-derived cytokines are involved in the development and invasion of pancreatic and head and neck cancers (4,5,23,24), however, the role of tumor-derived cytokines in the invasion of cervical cancer is not well understood. Furthermore, it has been demonstrated that the expression of brain-derived neurotrophic factor and its receptor TrkB may be involved in the development and invasion of cervical cancer (25).…”

Section: Discussionmentioning

confidence: 99%

“…It was first reported in European literature during the mid-1800s by scientists who described head and neck cancer that exhibited a predilection for growth along nerves as they made their way toward the intracranial fossa (1). PNI has since emerged as a prognostic factor in numerous malignancies, including head and neck, pancreatic cancer, prostate and gastrointestinal cancer types (2)(3)(4)(5). PNI has been generally accepted as a poor prognostic factor in head and neck squamous cell carcinoma (HNSCC) (6).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the association between perineural invasion and clinical and histopathological features of cervical cancer

Wei

Yao

Liu

2016

Molecular and Clinical Oncology

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Abstract. Perineural invasion (PNI) has been investigated as a new prognostic factor in a number of carcinomas. However, studies on PNI in cervical cancer are limited, and inconsistent conclusions have been reported by different groups. The aim of the present study was to analyze the relationship between perineural invasion (PNI) and clinical and histopathological features of cervical cancer, and to evaluate the clinical significance of PNI of cervical cancer. Retrospective review identified 206 patients with cervical cancer who underwent radical hysterectomy plus pelvic lymphadenectomy between December 2012 and August 2014. The association between PNI and clinical and histopathological features of cervical cancer and post-operative radiotherapy was evaluated based on univariate and multivariate analyses. PNI of cervical cancer was identified in 33 of 206 (16%) cervical cancer patients. Univariate analysis demonstrated that PNI was associated with clinical stage, tumor grade, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis (P<0.05), but not associated with age and histopathological types (P>0.05). Multivariate analysis suggests that LVSI and lymph node metastasis were associated with PNI of cervical cancer (P<0.05). In addition, post-operative radiotherapy was significantly more recommended for patients with PNI than those without PNI (P<0.001). In conclusion, PNI of cervical cancer is associated with LVSI and lymph node metastasis and can be used as an index for the determination of post-operative radiotherapy for cervical cancer patients.

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Neural Invasion in Pancreatic Cancer: The Past, Present and Future

Cited by 92 publications

References 45 publications

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker

Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling

Evaluation of the association between perineural invasion and clinical and histopathological features of cervical cancer

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