Serum amyloid A and inflammasome activation: A link to breast cancer progression?. (June 2021)

• Record Type: Journal Article
• Authors: Fourie, Carla; Shridas, Preetha; Davis, Tanja; de Villiers, Willem J.S.; Engelbrecht, Anna-Mart
• Is Part Of: Cytokine & growth factor reviews. Volume 59(2021)
• Page Start: 62
• Page End: 70
• Publication Date: 2021-06
• Subjects: CAF cancer associated fibroblast -- COX-2 cyclooxygenase-2 -- DAMP damage associated molecular pattern -- ECM extracellular matrix -- EMT epithelial-mesenchymal transition -- IL-1β interleukin 1 beta -- GSDMD gasdermin D -- MAPK mitogen activated protein kinase -- MMP-9 matrix metallopeptidase 9 -- NLRP3 nod-like receptor 3 -- PAMP pathogen associated molecular pattern -- PRR pattern recognition receptor -- TLR toll like receptor -- TME tumour microenvironment -- SAA serum amyloid A; Breast cancer -- Inflammasome -- Interleukin-1 -- Toll-like receptor -- Serum amyloid A; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2020.10.006
• Languages: English
• ISSNs: 1359-6101

Abstract

Highlights: In the tumour microenvironment (TME), the binding of serum amyloid a (SAA) to toll like receptors (TLRs) activates the inflammasome in several cancer types. Inflammasome activation results in the significant increase in interleukin-1β production. Once interleukin-1β is secreted into the TME, it creates a favorable pro-inflammatory environment to promote tumour growth, however, the exact mechanisms in breast cancer models remain to be elucidated. It is therefore plausible that in the TME, SAA functions as a damage associated molecular pattern (DAMP) that binds to TLRs on several cell types including cancer cells, immune cells and cancer associated fibroblasts. Once it is bound, the inflammasome is activated, which results in the secretion of interleukin-1β, contributing to tumour growth and ultimately metastasis. Therefore, by inhibiting the activation of the inflammasome or by producing neutralizing antibodies that target SAA, beneficial therapeutic approaches could arise for breast cancer patients. Abstract: Breast cancer is the most frequently diagnosed cancer in women globally. Although there have been many significant advances made in the diagnosis and treatment of breast cancer, numerous unresolved challenges remain, which include prevention, early diagnosis, metastasis and recurrence. The role of inflammation in cancer development is well established and is believed to be one of the leading hallmarks of cancer progression. Recently, the role of the inflammasome, a cytosolic multiprotein complex, has received attention in different cancers. By contributing to the activation of inflammatory cytokines the inflammasome intensifies the inflammatory cascade. The inflammasome can be activated through several pathways, which include the binding of pattern associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) to toll-like receptors (TLRs). Serum amyloid A (SAA), a non-specific acute-phase protein, can function as an endogenous DAMP by binding to pattern recognition receptors like TLRs on both breast cancer cells and cancer associated fibroblasts (CAFs). SAA can thus stimulate the production of IL-1β, thereby creating a favourable inflammatory environment to support tumour growth. The aim of this review is to highlight the possible role of SAA as an endogenous DAMP in the tumour microenvironment (TME) thereby promoting breast cancer growth through the activation of the NLRP3 inflammasome.