Ablation of sensory nerves favours melanoma progression

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 17; pp. 9574 - 9589
• Main Authors: Prazeres, Pedro H. D. M., Leonel, Caroline, Silva, Walison N., Rocha, Beatriz G. S., Santos, Gabryella S. P., Costa, Alinne C., Picoli, Caroline C., Sena, Isadora F. G., Gonçalves, William A., Vieira, Mariana S., Costa, Pedro A. C., Campos, Leda M. C. C., Lopes, Miriam T. P., Costa, Marcos R., Resende, Rodrigo R., Cunha, Thiago M., Mintz, Akiva, Birbrair, Alexander
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-09-2020; John Wiley and Sons Inc
• Subjects: Ablation; Animals; Cancer; Cell Communication - physiology; Cell culture; Cell Line, Tumor; Confocal microscopy; Denervation; Disease Progression; Experiments; genetic depletion; Humans; Melanoma; Melanoma - pathology; Mice; Mice, Inbred C57BL; Nervous system; Original; Retrospective Studies; sensory nerves; Sensory neurons; Sensory Receptor Cells - pathology; Skin Neoplasms - pathology; Tumor Microenvironment; Tumors; tumour microenvironment; Fiji; genetic depletion; melanoma; tumour microenvironment; sensory nerves
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.15381

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.