Petrilli Virginie
aINSERM U1052 bCNRS UMR5286, Centre de Recherche en Cancérologie de Lyon cUniversité de Lyon, Université Lyon 1 dCentre Léon Bérard, Lyon, France.
Curr Opin Oncol. 2017 Jan;29(1):35-40. doi: 10.1097/CCO.0000000000000346.
Inflammasomes are major actors of the innate immune system, through their regulation of inflammatory caspases and maturation of IL-1β and IL-18. These multiprotein complexes have been shown to play major roles in inflammatory and metabolic diseases and have more recently been implicated in tumor development and dissemination. In this review, we address these recent findings, focusing particularly on colorectal cancer (CRC) initiation and tumor dissemination.
Based mostly on loss-of-function experiments in mouse models, paradoxical results were obtained as both protumoral and antitumoral activities were reported. Moreover, several studies report major inflammasome-independent functions for some of these innate receptor proteins such as absent in melanoma 2, nod-like receptor family pyrin containing 3 (NLRP3) or nod-like receptor family CARD containing 4 (NLRC4), functions exerted in epithelial cells as well as in immune cells.
The current review summarizes recent findings on the implication of inflammasomes and of absent in melanoma 2, NLRC4 and NLRP3 inflammasome-independent functions in cancer development and dissemination. Although contradictory in certain aspects, these studies highlight a lack of understanding of their mechanistic functions and regulations in cancer and the need for further investigations.
炎性小体是固有免疫系统的主要参与者,通过调节炎性半胱天冬酶以及白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)的成熟发挥作用。这些多蛋白复合物已被证明在炎症和代谢性疾病中起主要作用,最近还与肿瘤的发生和扩散有关。在本综述中,我们阐述这些最新发现,尤其关注结直肠癌(CRC)的起始和肿瘤扩散。
主要基于小鼠模型中的功能丧失实验,得出了矛盾的结果,因为既有促肿瘤作用又有抗肿瘤作用的报道。此外,多项研究报告了其中一些固有受体蛋白(如黑色素瘤缺失因子2、含pyrin结构域的NOD样受体家族3(NLRP3)或含CARD结构域的NOD样受体家族4(NLRC4))具有不依赖炎性小体的主要功能,这些功能在上皮细胞和免疫细胞中均有发挥。
本综述总结了炎性小体以及黑色素瘤缺失因子2、NLRC4和NLRP3不依赖炎性小体的功能在癌症发生和扩散中的作用的最新发现。尽管在某些方面存在矛盾,但这些研究凸显了对它们在癌症中的机制功能和调控缺乏了解,以及进一步研究的必要性。