EVIDENCE FOR INFLAMMASOME ACTIVATION IN BREAST CANCER CELLS BY NEUTROPHIL EXTRACELLULAR TRAPS (NETs)

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  • Presentation type: DR - Doctoral Student
  • Track:
  • Keywords: NETs; INFLAMMASOME; Câncer;
  • 1 Universidade Federal do Rio de Janeiro
  • 2 Fundação Oswaldo Cruz

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Abstract

INTRODUCTION AND OBJECTIVES: Components of the immune system, such as Neutrophil Extracellular Traps (NETs) and inflammasomes, may favor the development and progression of cancer. A correlation between these two mechanisms, where the activation of one depends on the other, has already been shown in diseases such as lupus erythematosus and in diabetes, but in the context of cancer, such phenomenon has never been documented. Here we evaluated whether isolated NETs could upregulate elements of the inflammasome pathway in human breast carcinoma cell lines. MATERIAL AND METHODS: Human breast cancer cell lines MDA-MB-231 and MCF7 were stimulated with NETs isolated from PMA-treated neutrophils. Cultured cells were starved in serum-free medium and further treated with isolated NETs for 16 hours and the expression of the inflammasome genes was analyzed by qPCR. ELISA was employed to assess the release of interleukin-1 (IL-1β). RNA-seq data from breast cancer patients deposited in The Cancer Genome Atlas (TCGA) database were assessed. RESULTS AND CONCLUSION: An increase in the gene expression of NLRP3, CASP1 (caspase1) and IL1B (IL-1β) was observed in tumor cells treated with NETs, as compared to unstimulated cells. The release of IL-1β by tumor cells stimulated by NETs was also observed. TCGA analysis showed increased expression of inflammasome-related genes in more aggressive breast cancer subtypes, suggesting the upregulation of this pro-inflammatory pathway. We conclude that NETs may be an important determinant for inflammasome pathway in tumor cells, thus contributing to their pro-tumoral role.

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