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Serum amyloid A and inflammasome activation: A link to breast cancer progression?
Cytokine & Growth Factor Reviews ( IF 9.3 ) Pub Date : 2020-10-27 , DOI: 10.1016/j.cytogfr.2020.10.006
Carla Fourie 1 , Preetha Shridas 2 , Tanja Davis 1 , Willem J S de Villiers 3 , Anna-Mart Engelbrecht 4
Affiliation  

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.



中文翻译:

血清淀粉样蛋白 A 和炎症小体激活:与乳腺癌进展的联系?

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取得了许多重大进展,但仍有许多未解决的挑战,包括预防、早期诊断、转移和复发。炎症在癌症发展中的作用是公认的,并且被认为是癌症进展的主要标志之一。最近,炎症小体(一种胞质多蛋白复合物)在不同癌症中的作用受到关注。通过促进炎性细胞因子的激活,炎性体加强了炎症级联反应。炎症小体可以通过多种途径被激活,其中包括模式相关分子模式 (PAMP) 和损伤相关分子模式 (DAMP) 与 Toll 样受体 (TLR) 的结合。血清淀粉样蛋白 A (SAA) 是一种非特异性急性期蛋白,可通过与模式识别受体(如乳腺癌细胞和癌症相关成纤维细胞 (CAF) 上的 TLRs)结合而起到内源性 DAMP 的作用。因此,SAA 可以刺激 IL-1β 的产生,从而创造有利的炎症环境以支持肿瘤生长。本综述的目的是强调 SAA 作为内源性 DAMP 在肿瘤微环境 (TME) 中的可能作用,从而通过激活 NLRP3 炎性体促进乳腺癌生长。通过与乳腺癌细胞和癌症相关成纤维细胞 (CAF) 上的 TLR 等模式识别受体结合,可以起到内源性 DAMP 的作用。因此,SAA 可以刺激 IL-1β 的产生,从而创造有利的炎症环境以支持肿瘤生长。本综述的目的是强调 SAA 作为内源性 DAMP 在肿瘤微环境 (TME) 中的可能作用,从而通过激活 NLRP3 炎性体促进乳腺癌生长。通过与乳腺癌细胞和癌症相关成纤维细胞 (CAF) 上的 TLR 等模式识别受体结合,可以起到内源性 DAMP 的作用。因此,SAA 可以刺激 IL-1β 的产生,从而创造有利的炎症环境以支持肿瘤生长。本综述的目的是强调 SAA 作为内源性 DAMP 在肿瘤微环境 (TME) 中的可能作用,从而通过激活 NLRP3 炎性体促进乳腺癌生长。

更新日期:2020-10-30
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