The pancreatic innervation undergoes dynamic remodeling during the development of pancreatic ductal adenocarcinoma (PDAC). Denervation experiments have shown that different types of axons can exert either pro- or anti-tumor effects, but conflicting results exist in the literature, leaving the overall influence of the nervous system on PDAC incompletely understood. To address this gap, we propose a continuous mathematical model of nerve-tumor interactions that allows in silico simulation of denervation at different phases of tumor development. This model takes into account the pro- or anti-tumor properties of different types of axons (sympathetic or sensory) and their distinct remodeling dynamics during PDAC development. We observe a "shift effect" where an initial pro-tumor effect of sympathetic axon denervation is later outweighed by the anti-tumor effect of sensory axon denervation, leading to a transition from an overall protective to a deleterious role of the nervous system on PDAC tumorigenesis. Our model also highlights the importance of the impact of sympathetic axon remodeling dynamics on tumor progression. These findings may guide strategies targeting the nervous system to improve PDAC treatment.

翻译：胰腺导管腺癌（PDAC）发展过程中，胰腺神经支配会经历动态重塑。去神经实验表明，不同类型的轴突可发挥促肿瘤或抗肿瘤效应，但文献中存在相互矛盾的结果，导致神经系统对PDAC的整体影响尚未完全阐明。为填补这一空白，我们提出一个神经-肿瘤相互作用的连续数学模型，可在计算机上模拟肿瘤不同发展阶段的去神经过程。该模型考虑了不同类型轴突（交感或感觉）的促/抗肿瘤特性及其在PDAC发展过程中的差异性重塑动态。我们观察到一种"转移效应"：交感轴突去神经的初期促肿瘤作用随后被感觉轴突去神经的抗肿瘤作用所超越，导致神经系统对PDAC肿瘤发生的整体保护性作用转变为有害作用。该模型还揭示了交感轴突重塑动力学对肿瘤进展影响的重要性。这些发现可为靶向神经系统的PDAC治疗策略提供指导。