Papel das fibras nervosas sensoriais na progressão de tumores de mama, no modelo de câncer de mama murino E0771

Abstract

The global cancer panorama demonstrates a worrying upward trend in new cases, almost doubling in 2020 compared to 2000, in addition to the significant increase in deaths, representing on average one in every six in 2020. The number of women diagnosed with breast cancer jumped from 2.3 million at the beginning of 2020 to 7.8 million at the end of the same year, surpassing lung cancer. For Brazil, the National Cancer Institute forecasts for the triennium 2023-2025 more than 74,000 new cases of breast cancer per year. This exploratory study investigated the effects of activating Nav1.8 sensory nerve fibers in the context of breast cancer. Using the Nav1.8-Cre+/hM3Dq mouse model, where sensory nerve fibers were stimulated through the administration of CNO (clozapine-N-oxide). The experiment consisted of the orthotopic inoculation of E0771 cells in the mammary adipose tissue of mice, which were evaluated 28 days after cell inoculation. The results indicated that the activation of Nav1.8 sensory nerve fibers caused remarkable changes in the tumor microenvironment, in addition to a significant change in tumor volume, in response to the activation of these fibers. Furthermore, there was a notable reconfiguration in the expression of key molecules in the epithelial mesenchymal transition mechanism, such as E-cadherin, N-cadherin, Fibronectin and collagen fibers of the extracellular matrix. The activation of sensory nerve fibers also influenced cell proliferation rates. Intriguingly, the study revealed changes in liver metastases and suggested a possible migration of tumor cells to the lung. Through radiation uptake quantification techniques using HYNIC-βAla-Bombesin(7-14) peptide complex radiolabeled with 99Tc, no significant quantifications of metastasis were observed in distant organs, such as pancreas, brain, spleen and heart, however, further analysis of the formation of metastatic sites in this model are indicated. These results highlight the critical importance of sensory innervation in the progression of breast cancer. Keywords: cell biology; breast neoplasms; nervous system; nerve fibers; tumor microenvironment; metastasis.