Ablation of sensory nerves favours melanoma progression

Abstract

The tumour mass is composed not only of heterogeneous neoplastic cells, but also a variety of other components that may affect cancer cells behaviour. The lack of detailed knowledge about all the constituents of the tumour microenvironment restricts the design of effective treatments. Nerves have been reported to contribute to the growth and maintenance of numerous tissues. The effects of sensory innervations on tumour growth remain unclear. Here, by using state‐of‐the‐art techniques, including Cre/loxP technologies, confocal microscopy, in vivo‐tracing and chemical denervation, we revealed the presence of sensory nerves infiltrating within the melanoma microenvironment, and affecting cancer progression. Strikingly, melanoma growth in vivo was accelerated following genetic ablation or chemical denervation of sensory nerves. In humans, a retrospective analysis of melanoma patients revealed that increased expression of genes related to sensory nerves in tumours was associated with better clinical outcomes. These findings suggest that sensory innervations counteract melanoma progression. The emerging knowledge from this research provides a novel target in the tumour microenvironment for therapeutic benefit in cancer patients.

Sensory nerves in the spotlight of the stem cell niche

“…Classically, sensory nerves have been associated with tumor‐associated pain 163,164 . Interestingly, a new study shows that sensory nerve fibers are involved in tumor progression in vivo 124 . The authors show, by using Nav1.8‐Cre/TdTomato mice, the presence of sensory nerves within the tumor microenvironment.…”

“…Nonetheless, it will be important to examine whether sensory nerves can regulate hematopoietic stem cells also independently from their effect on BMSCs. As sensory nerves innervate multiple organs, 124 future studies should explore the role of these nerves in stem cell niches of other organs.…”

“…Prazeres and colleagues specifically depleted sensory innervations within the tumor microenvironment, in a model of genetic depletion of Nav1.8+ sensory neuronal projections or by chemical depletion using resiniferatoxin. These experiments revealed that sensory nerve ablation induces changes that lead to worse outcomes in tumor‐bearing mice 124 . Moreover, low expression of genes related to sensory nerves correlate with worse outcomes in human melanoma biopsies 124 .…”

“…Sensory neuronal projections infiltrate the tumor microenvironment. The study of Prazeres and colleagues indicates that sensory nerves block cancer progression 124 . Cellular and molecular mechanisms by which sensory nerves influence cancer development remain uncertain.…”

“…163,164 Interestingly, a new study shows that sensory nerve fibers are involved in tumor progression in vivo. 124 (Figure 3).…”