Role of the Nervous System in Cancer Development and Progression

Summary The nervous system governs functional activities of many organs. Solid tumour like organs are also innervated by nerve fibers. The nervous system can modulate angiogenesis, the tumor microenvironment, immune functions and inflammatory pathways to influence metastases. Peripheral nerve invasion provides an alternative pathway for the spread of cancer cells when blood and lymphatic metastases are absent.

Project Details

It is reasonable to hypothesize that different stages of cancer progression may be controlled by the changes in different types of nerve fibers, receptors and neurotransmitters influencing the immune response, tumour microenvironment and angiogenesis. Moreover, anti-cancer chemotherapy might modify these neutrally-induced processes, in some cases leading to chemotherapy-resistant tumourigenesis.

Aims of this study: In the colon tissues from animal models and patients with primary and metastatic colorectal cancer:

To determine the changes in innervation correlated to the different stages of cancer development and progression.

To investigate the interaction between innervation, immune cells, inflammatory mediators and tumour progression.

To understand the role of the nerve fiber proliferation in tumour angiogenesis.

To study the effects of anti-cancer chemotherapy on the colon innervation and the role of chemotherapy-induced oxidative stress in neurally-induced angiogenesis.

Significance of the project:

Despite the increasing interest to the role of the nervous system in cancer development and progression, the knowledge in this area is scarce. The blockers for α- and β-adrenergic receptors and neurotransmitter antagonists have exhibited promising anti-tumour activities in experimental studies. Further elucidation of the molecular mechanisms will provide better understanding of the relationship between innervation, immune system, and tumour progression. Revealing the interplay between the nervous and immune systems in cancer may open new avenues for understanding mechanisms of tumour development and progression, identification of new biomarkers for cancer diagnosis and prognosis, and defining novel targets for therapeutic interventions.