Fourie Carla, Shridas Preetha, Davis Tanja, de Villiers Willem J S, Engelbrecht Anna-Mart
Department of Physiological Sciences, Science Faculty, Stellenbosch University, Stellenbosch, South Africa.
Department of Internal Medicine, University of Kentucky, University of Kentucky, Kentucky, 40536, USA.
Cytokine Growth Factor Rev. 2021 Jun;59:62-70. doi: 10.1016/j.cytogfr.2020.10.006. Epub 2020 Oct 27.
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.
乳腺癌是全球女性中最常被诊断出的癌症。尽管在乳腺癌的诊断和治疗方面已经取得了许多重大进展，但仍存在许多未解决的挑战，包括预防、早期诊断、转移和复发。炎症在癌症发展中的作用已得到充分证实，并且被认为是癌症进展的主要标志之一。最近，炎性小体（一种胞质多蛋白复合物）在不同癌症中的作用受到了关注。通过促进炎性细胞因子的激活，炎性小体加剧了炎症级联反应。炎性小体可通过多种途径被激活，其中包括模式识别相关分子模式（PAMPs）和损伤相关分子模式（DAMPs）与Toll样受体（TLRs）的结合。血清淀粉样蛋白A（SAA）是一种非特异性急性期蛋白，可通过与乳腺癌细胞和癌症相关成纤维细胞（CAFs）上的TLRs等模式识别受体结合，作为内源性DAMP发挥作用。因此，SAA可刺激IL-1β的产生，从而营造一个有利于肿瘤生长的炎性环境。本综述的目的是强调SAA作为肿瘤微环境（TME）中的内源性DAMP，通过激活NLRP3炎性小体从而促进乳腺癌生长的可能作用。
