Neuronal signatures in cancer

Abstract

Despite advances in the treatment of solid tumors, the prognosis of patients with many cancers remains poor, particularly of those with primary and metastatic brain tumors. In the last years, "Cancer Neuroscience" emerged as novel field of research at the crossroads of oncology and classical neuroscience. In primary brain tumors, including glioblastoma (GB), communicating networks that render tumor cells resistant against cytotoxic therapies were identified. To build these networks, GB cells extend neurite-like protrusions called tumor microtubes (TMs). Synapses on TMs allow tumor cells to retrieve neuronal input that fosters growth. Single cell sequencing further revealed that primary brain tumors recapitulate many steps of neurodevelopment. Interestingly, neuronal characteristics, including the ability to extend neurite-like protrusions, neuronal gene expression signatures and interactions with neurons, have now been found not only in brain and neuroendocrine tumors but also in some cancers of epithelial origin. In this review, we will provide an overview about neurite-like protrusions as well as neurodevelopmental origins, hierarchies and gene expression signatures in cancer. We will also discuss how "Cancer Neuroscience" might provide a framework for the development of novel therapies.

A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression

“…Expression of neuronal genes has now been found not only in the brain and neuroendocrine tumors, but also in some cancers of epithelial origin (breast, ovary, colon) 65 . In recent years, it has become clear that tumor cells exploit neuronal and neurodevelopmental pathways to proliferate, migrate, and interact with normal cells, including endothelial cells and neurons 65 , 66 . Therefore, the overexpression of neuronal genes that we found in subtype 2 tumors may contribute to the aggressiveness of these tumors.…”

Many Voices in a Choir: Tumor-Induced Neurogenesis and Neuronal Driven Alternative Splicing Sound Like Suspects in Tumor Growth and Dissemination

“…A relationship between tumors and the nervous system has been suspected for a long time (since Galen in the 2nd century AD) [ 3 ], because of several observations such as the effects of stress on cancer progression, the high innervation of tumor tissues, or the influence that neurotransmitters have on tumorigenesis [ 4 , 5 ]. New evidence strongly suggests the neuronal system is a key player in cancer initiation, progression and dissemination [ 5 , 6 ]. It is believed that in the same way that the nervous system can influences growth, development, and maintenance in normal tissue [ 7 , 8 , 9 ], it can contribute to the development and spread of cancer [ 5 , 10 , 11 ].…”

Neurobiology of Cancer: Introduction of New Drugs in the Treatment and Prevention of Cancer

“…There are several sources of nerves in cancer tissue, including nerves already present in tissue before the transformation of normal tissue cells into cancer, phenotypically transformed neurons that innervate the tissue of tumor origin [ 119 ], new branches of nerves growing to the tumor tissue from nerves localized around the tumor tissue, and axons of new neurons migrating from a distant part of the central or peripheral nervous system into the tumor tissue or its vicinity [ 120 ]. The main stimuli for the ingrowth of new nerves into cancer tissue are nerve growth factors released by cells in the tumor microenvironment [ 121 ].…”

“…Signals, in the form of action potentials transmitted along the axons of autonomic and sensory neurons, participate in the modulation of cancer growth, as well as in the modulation of nervous system function by cancer. Besides electrical signals transmitted along axons, it has been shown that cancer cells may develop neurite-like protrusions that form contact with nerve endings [ 121 ], and that voltage-gated sodium channels play a role in cancer cell invasion and metastasis [ 138 , 139 ]. Therefore, it might be hypothesized that modulation of the electrical properties of cancer tissue and its vicinity might affect its progression.…”